Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
CNS Drugs
Published in: CNS Drugs 6/2015

01-06-2015 | Review Article

Targeting Opioid-Induced Hyperalgesia in Clinical Treatment: Neurobiological Considerations

Authors: Caroline A. Arout, Ellen Edens, Ismene L. Petrakis, Mehmet Sofuoglu

Published in: CNS Drugs | Issue 6/2015

Login to get access

Abstract

Opioid analgesics have become a cornerstone in the treatment of moderate to severe pain, resulting in a steady rise of opioid prescriptions. Subsequently, there has been a striking increase in the number of opioid-dependent individuals, opioid-related overdoses, and fatalities. Clinical use of opioids is further complicated by an increasingly deleterious profile of side effects beyond addiction, including tolerance and opioid-induced hyperalgesia (OIH), where OIH is defined as an increased sensitivity to already painful stimuli. This paradoxical state of increased nociception results from acute and long-term exposure to opioids, and appears to develop in a substantial subset of patients using opioids. Recently, there has been considerable interest in developing an efficacious treatment regimen for acute and chronic pain. However, there are currently no well-established treatments for OIH. Several substrates have emerged as potential modulators of OIH, including the N-methyl-D-aspartate and γ-aminobutyric acid receptors, and most notably, the innate neuroimmune system. This review summarizes the neurobiology of OIH in the context of clinical treatment; specifically, we review evidence for several pathways that show promise for the treatment of pain going forward, as prospective adjuvants to opioid analgesics. Overall, we suggest that this paradoxical state be considered an additional target of clinical treatment for chronic pain.
Literature
1.
Albutt C. On the abuse of hypodermic injections of morphia. Practitioner. 1870;3:327–30.
2.
Gaskin DJ, Richard P. The economic costs of pain in the United States. J Pain. 2012;13(8):715–24.PubMed
3.
Reuben DB, Alvanzo AAH, Ashikaga T, Bogat GA, Callahan CM, Ruffing V, et al. National Institutes of Health Pathways to Prevention Workshop: the role of opioids in the treatment of chronic pain. Ann Intern Med. 2015;162(4):295–300.PubMed
4.
Dureja GP, Jain PN, Shetty N, Mandal SP, Prabhoo R, Joshi M, et al. Prevalence of chronic pain, impact on daily life, and treatment practices in India. Pain Pract. 2014;14(2):E51–62.PubMed
5.
Ekholm O, Kurita GP, Højsted J, Juel K, Sjøgren P. Chronic pain, opioid prescriptions, and mortality in Denmark: a population-based cohort study. PAIN®. 2014;155(12):2486–90.
6.
Henderson JV, Harrison CM, Britt HC, Bayram CF, Miller GC. Prevalence, causes, severity, impact, and management of chronic pain in Australian general practice patients. Pain Med. 2013;14(9):1346–61.PubMed
7.
8.
Mehendale AW, Goldman MP, Mehendale RP. Opioid overuse pain syndrome (OOPS): the story of opioids, prometheus unbound. J Opioid Manag. 2013;9(6):421–38.
9.
Paulozzi LJ, Mack KA, Hockenberry JM. Vital signs: variation among states in prescribing of opioid pain relievers and benzodiazepines—United States, 2012. Morb Mortal Wkly Rep. 2014;26:563–8.
10.
Paulozzi LJ. Prescription drug overdoses: a review. J Saf Res. 2012;43(4):283–9.
11.
Manchikanti L, Abdi S, Atluri S, Balog CC, Benyamin RM, Boswell MV, et al. American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: part I—evidence assessment. Pain Phys. 2012;15(3 Suppl):S1–65.
12.
Sullivan MD, Howe CQ. Opioid therapy for chronic pain in the United States: promises and perils. PAIN®. 2013;154(Supplement 1):S94–S100.
13.
Manchikanti L, Damron K, McManus C, Barnhill R. Patterns of illicit drug use and opioid abuse in patients with chronic pain at initial evaluation: a prospective, observational study. Pain Physician. 2004;7(4):431–7.PubMed
14.
Edlund MJ. The role of opioid prescription in incident opioid abuse and dependence among individuals with chronic noncancer pain: the role of opioid prescription. Clin J Pain. 2014;30(7):557–64.
15.
16.
Fraud CAI. Prescription for peril: how insurance fraud finances theft and abuse of addictive prescription drugs. Washington, DC: Coalition Against Insurance Fraud; 2007.
17.
White AG, Birnbaum HG, Mareva MN, Daher M, Vallow S, Schein J, et al. Direct costs of opioid abuse in an insured population in the United States. J Manag Care Pharm. 2005;11(6):469.PubMed
18.
Benyamin R, Trescot AM, Datta S, Buenaventura R, Adlaka R, Sehgal N, et al. Opioid complications and side effects. Pain Physician. 2008;11(2 Suppl):S105–20.PubMed
19.
Ossipov MH, Lai J, Vanderah TW, Porreca F. Induction of pain facilitation by sustained opioid exposure: relationship to opioid antinociceptive tolerance. Life sci. 2003;73(6):783–800.PubMed
20.
Tompkins DA, Campbell CM. Opioid-induced hyperalgesia: clinically relevant or extraneous research phenomenon? Curr Pain Headache Rep. 2011;15(2):129–36.PubMedCentralPubMed
21.
Lee M, Silverman SM, Hansen H, Patel VB, Manchikanti L. A comprehensive review of opioid-induced hyperalgesia. Pain Physician. 2011;14(2):145–61.
22.
Chu LF, Angst MS, Clark D. Opioid-induced hyperalgesia in humans: molecular mechanisms and clinical considerations. Clin J Pain. 2008;24(6):479–96.PubMed
23.
Compton P, Kehoe P, Sinha K, Torrington MA, Ling W. Gabapentin improves cold-pressor pain responses in methadone-maintained patients. Drug Alcohol Depend. 2010;109(1):213–9.PubMedCentralPubMed
24.
Lee JS, Kim SG, Jeong HJ, Kim JH, Yang YH, Jung WY. Difference of the naltrexone’s effects in social drinkers by spicy food preference. J Korean Med Sci. 2014;29(5):714–8.PubMedCentralPubMed
25.
Eisenberg E, Suzan E, Pud D. Opioid-induced hyperalgesia (OIH): a real clinical problem or just an experimental phenomenon? J Pain Symptom Manag. 2014;49(3):632–6.
26.
Raffa RB, Pergolizzi Jr JV. Opioid-induced hyperalgesia: is it clinically relevant for the treatment of pain patients? Pain Manag Nurs. 2013;14(3):e67–e83.
27.
Heger S, Maier C, Otter K, Helwig U, Suttorp M, Berger A. Morphine induced allodynia in a child with brain tumour. BMJ. 1999;319(7210):627–9.PubMedCentralPubMed
28.
Low Y, Clarke CF, Huh BK. Opioid-induced hyperalgesia: a review of epidemiology, mechanisms and management. Singapore Med J. 2012;53(5):357–60.PubMed
29.
Holtman JR Jr, Jellish WS. Opioid-induced hyperalgesia and burn pain. J Burn Care Res. 2012;33(6):692–701.PubMed
30.
Chen L, Sein M, Vo T, Amhmed S, Zhang Y, Hilaire KS, et al. Clinical interpretation of opioid tolerance versus opioid-induced hyperalgesia. J Opioid Manag. 2014;10(6):383–93.
31.
Mao J, Sung B, Ji R-R, Lim G. Chronic morphine induces downregulation of spinal glutamate transporters: implications in morphine tolerance and abnormal pain sensitivity. J Neurosci. 2002;22(18):8312–23.PubMed
32.
Vanderah TW, Ossipov MH, Lai J, Malan TP Jr, Porreca F. Mechanisms of opioid-induced pain and antinociceptive tolerance: descending facilitation and spinal dynorphin. Pain. 2001;92(1–2):5–9.PubMed
33.
Vanderah TW, Suenaga NM, Ossipov MH, Malan TP Jr, Lai J, Porreca F. Tonic descending facilitation from the rostral ventromedial medulla mediates opioid-induced abnormal pain and antinociceptive tolerance. J Neurosci. 2001;21(1):279–86.PubMed
34.
Simonnet G, Rivat C. Opioid-induced hyperalgesia: abnormal or normal pain? Neuroreport. 2003;14(1):1–7.PubMed
35.
Ossipov MH, Lai J, King T, Vanderah TW, Malan TP, Hruby VJ, et al. Antinociceptive and nociceptive actions of opioids. J Neurobiol. 2004;61(1):126–48.PubMed
36.
Li Q. Antagonists of toll like receptor 4 maybe a new strategy to counteract opioid-induced hyperalgesia and opioid tolerance. Med Hypotheses. 2012;79(6):754–6.PubMed
37.
Watkins LR, Wiertelak EP, Goehler LE, Mooney-Heiberger K, Martinez J, Furness L, et al. Neurocircuitry of illness-induced hyperalgesia. Brain Res. 1994;639(2):283–99.PubMed
38.
Watkins LR, Hutchinson MR, Rice KC, Maier SF. The “toll” of opioid-induced glial activation: improving the clinical efficacy of opioids by targeting glia. Trends Pharmacol Sci. 2009;30(11):581–91.PubMedCentralPubMed
39.
Mercadante S, Ferrera P, Arcuri E, Casuccio A. Opioid-induced hyperalgesia after rapid titration with intravenous morphine: switching and re-titration to intravenous methadone. Ann Palliat Med. 2012;1(1):10–3.PubMed
40.
Ackerman WE 3rd. Paroxysmal opioid-induced pain and hyperalgesia. J Ky Med Assoc. 2006;104(9):419–23.PubMed
41.
Chu LF, Clark DJ, Angst MS. Opioid tolerance and hyperalgesia in chronic pain patients after one month of oral morphine therapy: a preliminary prospective study. The Journal of Pain. 2006;7(1):43–8.PubMed
42.
Juni A, Klein G, Kest B. Morphine hyperalgesia in mice is unrelated to opioid activity, analgesia, or tolerance: evidence for multiple diverse hyperalgesic systems. Brain Res. 2006;1070(1):35–44.PubMed
43.
Compton P, Canamar CP, Hillhouse M, Ling W. Hyperalgesia in heroin dependent patients and the effects of opioid substitution therapy. J Pain. 2012;13(4):401–9.PubMedCentralPubMed
44.
Waxman AR, Arout C, Caldwell M, Dahan A, Kest B. Acute and chronic fentanyl administration causes hyperalgesia independently of opioid receptor activity in mice. Neurosci Lett. 2009;462(1):68–72.PubMed
45.
Arout CA, Caldwell M, McCloskey DP, Kest B. C-Fos activation in the periaqueductal gray following acute morphine-3beta-d-glucuronide or morphine administration. Physiol Behav. 2014;10(130):28–33.
46.
Joly V, Richebe P, Guignard B, Fletcher D, Maurette P, Sessler DI, et al. Remifentanil-induced postoperative hyperalgesia and its prevention with small-dose ketamine. Anesthesiology. 2005;103(1):147–55.PubMed
47.
Chu LF, Cun T, Ngai LK, Kim JE, Zamora AK, Young CA, et al. Modulation of remifentanil-induced postinfusion hyperalgesia by the β-blocker propranolol in humans. Pain. 2012;153(5):974–81.PubMed
48.
Lenz H, Raeder J, Draegni T, Heyerdahl F, Schmelz M, Stubhaug A. Effects of COX inhibition on experimental pain and hyperalgesia during and after remifentanil infusion in humans. Pain. 2011;152(6):1289–97.PubMed
49.
Martinez V, Cymerman A, Ben Ammar S, Fiaud J, Rapon C, Poindessous F, et al. The analgesic efficiency of combined pregabalin and ketamine for total hip arthroplasty: a randomised, double-blind, controlled study. Anaesthesia. 2014;69(1):46–52.PubMed
50.
Sjøgren P, Jensen N-H, Jensen TS. Disappearance of morphine-induced hyperalgesia after discontinuing or substituting morphine with other opioid agonists. Pain. 1994;59(2):313–6.PubMed
51.
Cooper D, Lindsay S, Ryall D, Kokri M, Eldabe S, Lear G. Does intrathecal fentanyl produce acute cross-tolerance to iv morphine? Br J Anaesth. 1997;78(3):311–3.PubMed
52.
Chia Y-Y, Liu K, Wang J-J, Kuo M-C, Ho S-T. Intraoperative high dose fentanyl induces postoperative fentanyl tolerance. Can J Anesth. 1999;46(9):872–7.PubMed
53.
Guignard B, Bossard AE, Coste C, Sessler DI, Lebrault C, Alfonsi P, et al. Acute opioid tolerance: intraoperative remifentanil increases postoperative pain and morphine requirement. Anesthesiology. 2000;93(2):409–17.PubMed
54.
Yalcin N, Uzun ST, Reisli R, Borazan H, Otelcioglu S. A comparison of ketamine and paracetamol for preventing remifentanil induced hyperalgesia in patients undergoing total abdominal hysterectomy. Int J Med Sci. 2012;9(5):327.PubMedCentralPubMed
55.
Lee C, Lee H-W, Kim J-N. Effect of oral pregabalin on opioid-induced hyperalgesia in patients undergoing laparo-endoscopic single-site urologic surgery. Korean J Anesthesiol. 2013;64(1):19–24.PubMedCentralPubMed
56.
Koppert W, Schmelz M. The impact of opioid-induced hyperalgesia for postoperative pain. Best Pract Res Clin Anaesthesiol. 2007;21(1):65–83.PubMed
57.
Compton P, Charuvastra V, Ling W. Pain intolerance in opioid-maintained former opiate addicts: effect of long-acting maintenance agent. Drug Alcohol Depend. 2001;63(2):139–46.PubMed
58.
Doverty M, White JM, Somogyi AA, Bochner F, Ali R, Ling W. Hyperalgesic responses in methadone maintenance patients. Pain. 2001;90(1):91–6.PubMed
59.
Doverty M, Somogyi AA, White JM, Bochner F, Beare CH, Menelaou A, et al. Methadone maintenance patients are cross-tolerant to the antinociceptive effects of morphine. Pain. 2001;93(2):155–63.PubMed
60.
Pud D, Cohen D, Lawental E, Eisenberg E. Opioids and abnormal pain perception: New evidence from a study of chronic opioid addicts and healthy subjects. Drug Alcohol Depend. 2006;82(3):218–23.PubMed
61.
Fallon M, Colvin L. Opioid-induced hyperalgesia: fact or fiction? Palliat Med. 2008;22(1):5–6.PubMed
62.
Luginbühl M, Gerber A, Schnider TW, Petersen-Felix S, Arendt-Nielsen L, Curatolo M. Modulation of remifentanil-induced analgesia, hyperalgesia, and tolerance by small-dose ketamine in humans. Anesth Analg. 2003;96(3):726–32.PubMed
63.
Holtman J, Johnson J, Kelly T, Wala E. (663): Opioid-induced abnormal pain sensitivity. The Journal of Pain. 2007;8(4):S16.
64.
Koppert W, Sittl R, Scheuber K, Alsheimer M, Schmelz M, Schüttler J. Differential modulation of remifentanil-induced analgesia and postinfusion hyperalgesia by S-ketamine and clonidine in humans. Anesthesiology. 2003;99(1):152–9.PubMed
65.
Compton P, Athanasos P, Elashoff D. Withdrawal hyperalgesia after acute opioid physical dependence in nonaddicted humans: a preliminary study. J Pain. 2003;4(9):511–9.PubMed
66.
Lee SH, Cho SY, Lee HG, Choi JI, Yoon MH, Kim WM. Tramadol induced paradoxical hyperalgesia. Pain Physician. 2013;16(1):41–4.PubMed
67.
Hina N, Fletcher D, Poindessous-Jazat F, Martinez V. Hyperalgesia induced by low-dose opioid treatment before orthopaedic surgery: An observational case-control study. Eur J Anaesthesiol. 2015;32(4):255–61.PubMed
68.
Suzan E, Eisenberg E, Treister R, Haddad M, Pud D. A negative correlation between hyperalgesia and analgesia in patients with chronic radicular pain: is hydromorphone therapy a double-edged sword? Pain Physician. 2013;16(1):65–76.PubMed
69.
Hooten WM, Lamer TJ, Twyner C. Opioid-induced hyperalgesia in community-dwelling adults with chronic pain. Pain. 2015;156(6):1145–52.PubMed
70.
Pivec R, Issa K, Naziri Q, Kapadia BH, Bonutti PM, Mont MA. Opioid use prior to total hip arthroplasty leads to worse clinical outcomes. Int Orthop. 2014;38(6):1159–65.PubMedCentralPubMed
71.
Axelrod DJ, Reville B. Using methadone to treat opioid-induced hyperalgesia and refractory pain. J Opioid Manag. 2007;3(2):113–4.
72.
Monterubbianesi MC, Capuccini J, Ferioli I, Tassinari D, Sarti D, Raffaeli W. High opioid dosage rapid detoxification of cancer patient in palliative care with the Raffaeli model. J Opioid Manag. 2012;8(5):292–8.
73.
Pirbudak L, Sevinc A, Maralcan G, Kilic E. Pain management with intrathecal clonidine in a colon cancer patient with opioid hyperalgesia: case presentation. Agri : Agri (Algoloji) Dernegi’nin Yayin organidir = J Turk Soc Algol. 2014;26(2):93–6.
74.
Kaye AD, Alian AA, Vadivelu N, Chung KS. Perioperative dilemma: challenges of the management of a patient on mega doses of morphine and methadone. J Opioid Manag. 2014;10(1):69–72.
75.
Dumas EO, Pollack GM. Opioid tolerance development: a pharmacokinetic/pharmacodynamic perspective. The AAPS J. 2008;10(4):537–51.PubMed
76.
Yoburn BC, Cohen AH, Inturrisi CE. Pharmacokinetics and pharmacodynamics of subcutaneous naltrexone pellets in the rat. J Pharmacol Exp Ther. 1986;237(1):126–30.PubMed
77.
Juni A, Klein G, Pintar J, Kest B. Nociception increases during opioid infusion in opioid receptor triple knock-out mice. Neuroscience. 2007;147(2):439–44.PubMed
78.
Ferrini F, Trang T, Mattioli T-AM, Laffray S, Del’Guidice T, Lorenzo L-E, et al. Morphine hyperalgesia gated through microglia-mediated disruption of neuronal Cl- homeostasis. Nat Neurosci. 2013;16(2):183–92.
79.
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association; 2000.
80.
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA: American Psychiatric Association; 2013.
81.
82.
83.
Harris AC, Hanes SL, Gewirtz JC. Potentiated startle and hyperalgesia during withdrawal from acute morphine: effects of multiple opiate exposures. Psychopharmacology. 2004;176(3–4):266–73.PubMed
84.
Dunbar SA, Karamian I, Yeatman A, Zhang J. Effects of recurrent withdrawal on spinal GABA release during chronic morphine infusion in the rat. Eur J Pharmacol. 2006;535(1):152–6.PubMed
85.
Dunbar SA, Karamian I, Zhang J. Ketorolac prevents recurrent withdrawal induced hyperalgesia but does not inhibit tolerance to spinal morphine in the rat. Eur J Pain. 2007;11(1):1–6.
86.
Manchikanti L. Opioid-induced hyperalgesia method is a clinically relevant issue. Ann Palliat Med. 2012;1(1):2–3.PubMed
87.
Gutstein HB. The effects of pain on opioid tolerance: how do we resolve the controversy? Pharmacol Rev. 1996;48(3):403–7.PubMed
88.
Angst MS, Koppert W, Pahl I, Clark DJ, Schmelz M. Short-term infusion of the mu-opioid agonist remifentanil in humans causes hyperalgesia during withdrawal. Pain. 2003;106(1–2):49–57.PubMed
89.
Li X, Clark JD. Hyperalgesia during opioid abstinence: mediation by glutamate and substance p. Anesth Analg. 2002;95(4):979–84.PubMed
90.
Sjøgren P, Thunedborg L, Christrup L, Hansen S, Franks J. Is development of hyperalgesia, allodynia and myoclonus related to morphine metabolism during long-term administration?: Six case histories. Acta Anaesthesiol Scand. 1998;42(9):1070–5.PubMed
91.
Compton MA. Cold-pressor pain tolerance in opiate and cocaine abusers: correlates of drug type and use status. J Pain Symptom Manag. 1994;9(7):462–73.
92.
Weissman DE, Haddox JD. Opioid pseudoaddiction—an iatrogenic syndrome. Pain. 1989;36(3):363–6.
93.
Swartjes M, Mooren R, Waxman AR, Arout C, van de Wetering K, den Hartigh J, et al. Morphine-induced hyperalgesia develops without involvement of morphine-3-glucuronide and is prevented by selective and non-selective N-methyl-d-aspartate antagonists. Mol Med. 2012;18(1):1320–6.PubMedCentralPubMed
94.
Woolf CJ. Intrathecal high dose morphine produces hyperalgesia in the rat. Brain Res. 1981;209(2):491–5.PubMed
95.
Yaksh T, Harty G, Onofrio B. High dose of spinal morphine produce a nonopiate receptor-mediated hyperesthesia: clinical and theoretic implications. Anesthesiology. 1986;64(5):590–7.PubMed
96.
Sakurada T, Watanabe C, Okuda K, Sugiyama A, Moriyama T, Sakurada C, et al. Intrathecal high-dose morphine induces spinally-mediated behavioral responses through NMDA receptors. Mol Brain Res. 2002;98(1):111–8.PubMed
97.
Ji R-R, Kohno T, Moore KA, Woolf CJ. Central sensitization and LTP: do pain and memory share similar mechanisms? Trends Neurosci. 2003;26(12):696–705.PubMed
98.
Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011;152(3 Suppl):S2–15.PubMedCentralPubMed
99.
Mao J. Opioid-induced abnormal pain sensitivity: implications in clinical opioid therapy. Pain. 2002;100(3):213–7.PubMed
100.
King T, Gardell LR, Wang R, Vardanyan A, Ossipov MH. Role of NK-1 neurotransmission in opioid-induced hyperalgesia. Pain. 2005;116(3):276–88.PubMedCentralPubMed
101.
Nichols ML, Allen BJ, Rogers SD, Ghilardi JR, Honore P, Luger NM, et al. Transmission of chronic nociception by spinal neurons expressing the substance P receptor. Science. 1999;286(5444):1558–61.PubMed
102.
McCarthy PW, Lawson SN. Cell type and conduction velocity of rat primary sensory neurons with substance P-like immunoreactivity. Neuroscience. 1989;28(3):745–53.PubMed
103.
Duggan AW, Morton CR, Zhao ZQ, Hendry IA. Noxious heating of the skin releases immunoreactive substance P in the substantia gelatinosa of the cat: a study with antibody microprobes. Brain Res. 1987;403(2):345–9.PubMed
104.
Takeda Y, Chou KB, Takeda J, Sachais BS, Krause JE. Molecular cloning, structural characterization and functional expression of the human substance P receptor. Biochem Biophys Res Commun. 1991;179(3):1232–40.PubMed
105.
Gardell LR, Wang R, Burgess SE, Ossipov MH, Vanderah TW, Malan TP Jr, et al. Sustained morphine exposure induces a spinal dynorphin-dependent enhancement of excitatory transmitter release from primary afferent fibers. J Neurosci. 2002;22(15):6747–55.PubMed
106.
Wang Z, Gardell LR, Ossipov MH, Vanderah TW, Brennan MB, Hochgeschwender U, et al. Pronociceptive actions of dynorphin maintain chronic neuropathic pain. J Neurosci. 2001;21(5):1779–86.PubMed
107.
Laughlin TM, Vanderah TW, Lashbrook J, Nichols ML, Ossipov M, Porreca F, et al. Spinally administered dynorphin A produces long-lasting allodynia: involvement of NMDA but not opioid receptors. Pain. 1997;72(1–2):253–60.PubMed
108.
Laughlin TM, Bethea JR, Yezierski RP, Wilcox GL. Cytokine involvement in dynorphin-induced allodynia. Pain. 2000;84(2):159–67.PubMed
109.
Lai J, Ossipov MH, Vanderah TW, Malan TP Jr, Porreca F. Neuropathic pain: the paradox of dynorphin. Mol Interv. 2001;1(3):160–7.PubMed
110.
Vanderah TW, Gardell LR, Burgess SE, Ibrahim M, Dogrul A, Zhong CM, et al. Dynorphin promotes abnormal pain and spinal opioid antinociceptive tolerance. J Neurosci. 2000;20(18):7074–9.PubMed
111.
Vanderah TW, Laughlin T, Lashbrook JM, Nichols ML, Wilcox GL, Ossipov MH, et al. Single intrathecal injections of dynorphin A or des-Tyr-dynorphins produce long-lasting allodynia in rats: blockade by MK-801 but not naloxone. Pain. 1996;68(2–3):275–81.PubMed
112.
Deleo JA, Tanga FY, Tawfik VL. Neuroimmune activation and neuroinflammation in chronic pain and opioid tolerance/hyperalgesia. Neuroscientist. 2004;10(1):40–52.PubMed
113.
Coller JK, Hutchinson MR. Implications of central immune signaling caused by drugs of abuse: mechanisms, mediators and new therapeutic approaches for prediction and treatment of drug dependence. Pharmacol Ther. 2012;134(2):219–45.PubMed
114.
Hutchinson MR, Bland ST, Johnson KW, Rice KC, Maier SF, Watkins LR. Opioid-induced glial activation: mechanisms of activation and implications for opioid analgesia, dependence, and reward. Scientific World J. 2007;7:98–111.
115.
Hutchinson MR, Coats BD, Lewis SS, Zhang Y, Sprunger DB, Rezvani N, et al. Proinflammatory cytokines oppose opioid-induced acute and chronic analgesia. Brain Behav Immun. 2008;22(8):1178–89.PubMedCentralPubMed
116.
Hutchinson MR, Lewis SS, Coats BD, Rezvani N, Zhang Y, Wieseler JL, et al. Possible involvement of toll-like receptor 4/myeloid differentiation factor-2 activity of opioid inactive isomers causes spinal proinflammation and related behavioral consequences. Neuroscience. 2010;167(3):880–93.PubMedCentralPubMed
117.
Eidson LN, Murphy AZ. Blockade of toll-like receptor 4 attenuates morphine tolerance and facilitates the pain relieving properties of morphine. J Neurosci. 2013;33(40):15952–63.PubMedCentralPubMed
118.
Jacobsen J, Watkins LR, Hutchinson MR. Discovery of a novel site of opioid action at the innate immune pattern-recognition receptor TLR4 and its role in addiction. Int Rev Neurobiol. 2013;118:129–63.
119.
Hutchinson MR, Zhang Y, Shridhar M, Evans JH, Buchanan MM, Zhao TX, et al. Evidence that opioids may have toll-like receptor 4 and MD-2 effects. Brain Behav Immun. 2010;24(1):83–95.PubMedCentralPubMed
120.
Lewis SS, Hutchinson MR, Rezvani N, Loram LC, Zhang Y, Maier SF, et al. Evidence that intrathecal morphine-3-glucuronide may cause pain enhancement via toll-like receptor 4/MD-2 and interleukin-1β. Neuroscience. 2010;165(2):569–83.PubMedCentralPubMed
121.
Watkins LR, Maier SF, Goehler LE. Immune activation: the role of pro-inflammatory cytokines in inflammation, illness responses and pathological pain states. Pain. 1995;63(3):289–302.PubMed
122.
Hutchinson MR, Zhang Y, Brown K, Coats BD, Shridhar M, Sholar PW, et al. Non-stereoselective reversal of neuropathic pain by naloxone and naltrexone: involvement of toll-like receptor 4 (TLR4). Eur J Neurosci. 2008;28(1):20–9.PubMedCentralPubMed
123.
Narita M, Miyatake M, Narita M, Shibasaki M, Shindo K, Nakamura A, et al. Direct evidence of astrocytic modulation in the development of rewarding effects induced by drugs of abuse. Neuropsychopharmacology. 2006;31(11):2476–88.PubMed
124.
Horvath RJ, DeLeo JA. Morphine enhances microglial migration through modulation of P2X4 receptor signaling. J Neurosci. 2009;29(4):998–1005.PubMedCentralPubMed
125.
Takayama N, Ueda H. Morphine-induced chemotaxis and brain-derived neurotrophic factor expression in microglia. J Neurosci. 2005;25(2):430–5.PubMed
126.
Hutchinson MR, Northcutt A, Hiranita T, Wang X, Lewis S, Thomas J, et al. Opioid activation of toll-like receptor 4 contributes to drug reinforcement. J Neurosci. 2012;32(33):11187–200.PubMedCentralPubMed
127.
Hameed H, Hameed M, Christo PJ. The effect of morphine on glial cells as a potential therapeutic target for pharmacological development of analgesic drugs. Curr Pain Headache Rep. 2010;14(2):96–104.PubMed
128.
Wang X, Loram LC, Ramos K, de Jesus AJ, Thomas J, Cheng K, et al. Morphine activates neuroinflammation in a manner parallel to endotoxin. Proc Natl Acad Sci USA. 2012;109(16):6325–30.PubMedCentralPubMed
129.
Antonilli L, Petecchia E, Caprioli D, Badiani A, Nencini P. Effect of repeated administrations of heroin, naltrexone, methadone, and alcohol on morphine glucuronidation in the rat. Psychopharmacology. 2005;182(1):58–64.PubMed
130.
Stevens C, Aravind S, Das S, Davis R. Pharmacological characterization of LPS and opioid interactions at the toll-like receptor 4. Br J Pharmacol. 2013;168(6):1421–9.PubMedCentralPubMed
131.
Trujillo KA, Akil H. Inhibition of morphine tolerance and dependence by the NMDA receptor antagonist MK-801. Science. 1991;251(4989):85–7.PubMed
132.
Trujillo KA. Effects of noncompetitive N-methyl-d-aspartate receptor antagonists on opiate tolerance and physical dependence. Neuropsychopharmacology. 1995;13(4):301–7.PubMed
133.
Mao J, Price DD, Mayer DJ. Mechanisms of hyperalgesian and morphine tolerance: a current view of their possible interactions. Pain. 1995;62(3):259–74.PubMed
134.
De Kock M, Lavand’homme P, Waterloos H. ‘Balanced analgesia’in the perioperative period: is there a place for ketamine? Pain. 2001;92(3):373–80.PubMed
135.
Du J, Zhou S, Coggeshall R, Carlton S. N-methyl-d-aspartate-induced excitation and sensitization of normal and inflamed nociceptors. Neuroscience. 2003;118(2):547–62.PubMed
136.
Sluka K, Audette K. Activation of protein kinase C in the spinal cord produces mechanical hyperalgesia by activating glutamate receptors, but does not mediate chronic muscle-induced hyperalgesia. Mol Pain. 2006;2(13):1–9.
137.
Gladding CM, Raymond LA. Mechanisms underlying NMDA receptor synaptic/extrasynaptic distribution and function. Mol Cell Neurosci. 2011;48(4):308–20.PubMed
138.
Guignard B, Coste C, Costes H, Sessler DI, Lebrault C, Morris W, et al. Supplementing desflurane-remifentanil anesthesia with small-dose ketamine reduces perioperative opioid analgesic requirements. Anesth Analg. 2002;95(1):103–8.PubMed
139.
Zhao Y-L, Chen S-R, Chen H, Pan H-L. Chronic opioid potentiates presynaptic but impairs postsynaptic N-methyl-d-aspartic acid receptor activity in spinal cords implications for opioid hyperalgesia and tolerance. J Biol Chem. 2012;287(30):25073–85.PubMedCentralPubMed
140.
Kalyuzhny AE, Wessendorf MW. Relationship of μ-and δ-opioid receptors to GABAergic neurons in the central nervous system, including antinociceptive brainstem circuits. J Comp Neurol. 1998;392(4):528–47.PubMed
141.
Kalyuzhny AE, Dooyema J, Wessendorf MW. Opioid-and GABAA-receptors are co-expressed by neurons in rat brain. Neuroreport. 2000;11(12):2625–8.PubMed
142.
Watkins LR, Hutchinson MR, Ledeboer A, Wieseler-Frank J, Milligan ED, Maier SF. Norman cousins lecture. Glia as the “bad guys”: implications for improving clinical pain control and the clinical utility of opioids. Brain Behav Immun. 2007;21(2):131–46.PubMedCentralPubMed
143.
Cohen GA, Doze VA, Madison DV. Opioid inhibition of GABA release from presynaptic terminals of rat hippocampal interneurons. Neuron. 1992;9(2):325–35.PubMed
144.
Vaughan CW, Ingram SL, Connor MA, Christie MJ. How opioids inhibit GABA-mediated neurotransmission. Nature. 1997;390(6660):611–4.PubMed
145.
Patte-Mensah C, Meyer L, Taleb O, Mensah-Nyagan AG. Potential role of allopregnanolone for a safe and effective therapy of neuropathic pain. Prog Neurobiol. 2014;113:70–8.PubMed
146.
Schumacher M, Mattern C, Ghoumari A, Oudinet J, Liere P, Labombarda F, et al. Revisiting the roles of progesterone and allopregnanolone in the nervous system: resurgence of the progesterone receptors. Prog Neurobiol. 2014;113:6–39.PubMed
147.
Melcangi RC, Panzica GC. Allopregnanolone: state of the art. Prog Neurobiol. 2014;113:1–5.PubMed
148.
Zelcer N, van de Wetering K, Hillebrand M, Sarton E, Kuil A, Wielinga PR, et al. Mice lacking multidrug resistance protein 3 show altered morphine pharmacokinetics and morphine-6-glucuronide antinociception. Proc Natl Acad Sci USA. 2005;102(20):7274–9.PubMedCentralPubMed
149.
van Dorp EL, Kest B, Kowalczyk WJ, Morariu AM, Waxman AR, Arout CA, et al. Morphine-6beta-glucuronide rapidly increases pain sensitivity independently of opioid receptor activity in mice and humans. Anesthesiology. 2009;110(6):1356–63.PubMed
150.
Hammoud HA, Aymard G, Lechat P, Boccheciampe N, Riou B, Aubrun F. Relationships between plasma concentrations of morphine, morphine-3-glucuronide, morphine-6-glucuronide, and intravenous morphine titration outcomes in the postoperative period. Fundam Clin Pharmacol. 2011;25(4):518–27.PubMed
151.
Samuelsson H, Hedner T, Venn R, Michalkiewicz A. CSF and plasma concentrations of morphine and morphine glucuronides in cancer patients receiving epidural morphine. Pain. 1993;52(2):179–85.
152.
De Gregori S, Minella CE, De Gregori M, Tinelli C, Ranzani GN, Govoni S, et al. Clinical pharmacokinetics of morphine and its metabolites during morphine dose titration for chronic cancer pain. Ther Drug Monit. 2014;36(3):335–44.PubMed
153.
Li X, Angst MS, Clark JD. A murine model of opioid-induced hyperalgesia. Mol Brain Res. 2001;86(1):56–62.PubMed
154.
Fine PG, Portenoy RK. Establishing “Best Practices” for opioid rotation: conclusions of an expert panel. J Pain Symptom Manag. 2009;38(3):418–25.
155.
Juba KM, Wahler RG, Daron SM. Morphine and hydromorphone-induced hyperalgesia in a hospice patient. J Palliat Med. 2013;16(7):809–12.PubMed
156.
Vorobeychik Y, Chen L, Bush MC, Mao J. Improved opioid analgesic effect following opioid dose reduction. Pain Med (Malden, Mass). 2008;9(6):724–7.
157.
Wilson GR, Reisfield GM. Morphine hyperalgesia: a case report. Am J Hosp Palliat Care. 2003;20(6):459–61.
158.
de Conno F, Caraceni A, Martini C, Spoldi E, Salvetti M, Ventafridda V. Hyperalgesia and myoclonus with intrathecal infusion of high-dose morphine. Pain. 1991;47(3):337–9.PubMed
159.
Vorobeychik Y, Chen L, Bush MC, Mao J. Improved opioid analgesic effect following opioid dose reduction. Pain Med. 2008;9(6):724–7.PubMed
160.
Juni A, Cai M, Stankova M, Waxman AR, Arout C, Klein G, et al. Sex-specific mediation of opioid-induced hyperalgesia by the melanocortin-1 receptor. Anesthesiology. 2010;112(1):181–8.PubMed
161.
Juni A, Klein G, Kowalczyk B, Ragnauth A, Kest B. Sex differences in hyperalgesia during morphine infusion: effect of gonadectomy and estrogen treatment. Neuropharmacology. 2008;54(8):1264–70.PubMed
162.
Waxman AR, Juni A, Kowalczyk W, Arout C, Sternberg WF, Kest B. Progesterone rapidly recruits female-typical opioid-induced hyperalgesic mechanisms. Physiol Behav. 2010;101(5):759–63.PubMed
163.
Laulin JP, Celerier E, Larcher A, Le Moal M, Simonnet G. Opiate tolerance to daily heroin administration: an apparent phenomenon associated with enhanced pain sensitivity. Neuroscience. 1999;89(3):631–6.PubMed
164.
Laulin JP, Larcher A, Celerier E, Le Moal M, Simonnet G. Long-lasting increased pain sensitivity in rat following exposure to heroin for the first time. Eur J Neurosci. 1998;10(2):782–5.PubMed
165.
Laulin JP, Larcher A, Célèrier E, Moal ML, Simonnet G. Long-lasting increased pain sensitivity in rat following exposure to heroin for the first time. Eur J Neurosci. 1998;10(2):782–5.PubMed
166.
Hang L-H, Shao D-H, Gu Y-P. The ED50 and ED95 of ketamine for prevention of postoperative hyperalgesia after remifentanil-based anaesthesia in patients undergoing laparoscopic cholecystectomy. Swiss Med Wkly. 2011;141:w13195.PubMed
167.
Tröster A, Sittl R, Singler B, Schmelz M, Schuttler J, Koppert W. Modulation of remifentanil-induced analgesia and postinfusion hyperalgesia by parecoxib in humans. Anesthesiology. 2006;105(5):1016–23.PubMed
168.
Smith DJ, Pekoe GM, Martin LL, Coalgate B. The interaction of ketamine with the opiate receptor. Life Sci. 1980;26(10):789–95.PubMed
169.
Persson J. Ketamine in pain management. CNS Neurosci Ther. 2013;19(6):396–402.PubMed
170.
Max MB, Byas-Smith MG, Gracely RH, Bennett GJ. Intravenous infusion of the NMDA antagonist, ketamine, in chronic posttraumatic pain with allodynia: a double-blind comparison to alfentanil and placebo. Clin Neuropharmacol. 1995;18(4):360–8.PubMed
171.
Laulin J-P, Maurette P, Corcuff J-B, Rivat C, Chauvin M, Simonnet G. The role of ketamine in preventing fentanyl-induced hyperalgesia and subsequent acute morphine tolerance. Anesth Analg. 2002;94(5):1263–9.PubMed
172.
Swartjes M, Morariu A, Niesters M, Aarts L, Dahan A. Nonselective and NR2B-selective N-methyl-D-aspartic acid receptor antagonists produce antinociception and long-term relief of allodynia in acute and neuropathic pain. Anesthesiology. 2011;115(1):165–74.PubMed
173.
Tverskoy M, Oz Y, Isakson A, Finger J, Bradley EL Jr, Kissin I. Preemptive effect of fentanyl and ketamine on postoperative pain and wound hyperalgesia. Anesth Analg. 1994;78(2):205–9.PubMed
174.
Lavand’homme P, De Kock M, Waterloos H. Intraoperative epidural analgesia combined with ketamine provides effective preventive analgesia in patients undergoing major digestive surgery. Anesthesiology. 2005;103(4):813–20.
175.
Roytblat L, Korotkoruchko A, Katz J, Glazer M, Greemberg L, Fisher A. Postoperative pain: the effect of low-dose ketamine in addition to general anesthesia. Anesth Analg. 1993;77(6):1161–5.PubMed
176.
Wong C-S, Liaw W-J, Tung C-S, Su Y-F, Ho S-T. Ketamine potentiates analgesic effect of morphine in postoperative epidural pain control. Reg Anesth Pain Med. 1996;21(6):534–41.
177.
Fu ES, Miguel R, Scharf JE. Preemptive ketamine decreases postoperative narcotic requirements in patients undergoing abdominal surgery. Anesth Analg. 1997;84(5):1086–90.PubMed
178.
Menigaux C, Fletcher D, Dupont X, Guignard B, Guirimand F, Chauvin M. The benefits of intraoperative small-dose ketamine on postoperative pain after anterior cruciate ligament repair. Anesth Analg. 2000;90(1):129.PubMed
179.
Menigaux C, Guignard B, Fletcher D, Sessler DI, Dupont X, Chauvin M. Intraoperative small-dose ketamine enhances analgesia after outpatient knee arthroscopy. Anesth Analg. 2001;93(3):606–12.PubMed
180.
Zakine J, Samarcq D, Lorne E, Moubarak M, Montravers P, Beloucif S, et al. Postoperative ketamine administration decreases morphine consumption in major abdominal surgery: a prospective, randomized, double-blind, controlled study. Anesth Analg. 2008;106(6):1856–61.PubMed
181.
White PF, Way WL, Trevor AJ. Ketamine-its pharmacology and therapeutic uses. Anesthesiology. 1982;56:119–36.PubMed
182.
Holtman JR Jr, Crooks PA, Johnson-Hardy JK, Hojomat M, Kleven M, Wala EP. Effects of norketamine enantiomers in rodent models of persistent pain. Pharmacol Biochem Behav. 2008;90(4):676–85.PubMed
183.
Fanta S, Kinnunen M, Backman JT, Kalso E. Population pharmacokinetics of S-ketamine and norketamine in healthy volunteers after intravenous and oral dosing. Eur J Clin Pharmacol. 2015;71(4):441–7.PubMed
184.
Bredlau AL, Thakur R, Korones DN, Dworkin RH. Ketamine for pain in adults and children with cancer: a systematic review and synthesis of the literature. Pain Med. 2013;14(10):1505–17.PubMed
185.
Way WL. Ketamine-its pharmacology and therapeutic uses. Anesthesiology. 1982;56(2):119–36.PubMed
186.
Weinbroum AA, Rudick V, Paret G, Ben-Abraham R. The role of dextromethorphan in pain control. Can J Anesth. 2000;47(6):585–96.PubMed
187.
Ramasubbu C, Gupta A. Pharmacological treatment of opioid-induced hyperalgesia: a review of the evidence. J Pain Palliat Care Pharmacother. 2011;25(3):219–30.PubMed
188.
Elliott K, Kest B, Man A, Kao B, Inturrisi CE. N-methyl-d-aspartate (NMDA) receptors, mu and kappa opioid tolerance, and perspectives on new analgesic drug development. Neuropsychopharmacology. 1995;13(4):347–56.PubMed
189.
Popik P, Kozela E, Danysz W. Clinically available NMDA receptor antagonists memantine and dextromethorphan reverse existing tolerance to the antinociceptive effects of morphine in mice. Naunyn-Schmiedeberg’s Arch Pharmacol. 2000;361(4):425–32.
190.
Salehi M, Zargar A, Ramezani MA. Effects of dextromethorphan on reducing methadone dosage in opium addicts undergoing methadone maintenance therapy: A double blind randomized clinical trial. J Res Med Sci. 2011;16(10):1354.PubMedCentralPubMed
191.
Chen S-L, Lee S-Y, Tao P-L, Chang Y-H, Chen S-H, Chu C-H, et al. Dextromethorphan attenuated inflammation and Combined Opioid Use in Humans Undergoing Methadone Maintenance Treatment. J Neuroimmune Pharmacol. 2012;7(4):1025–33.PubMed
192.
Koyuncuoğlu H, Saydam B. The treatment of heroin addicts with dextromethorphan: a double-blind comparison of dextromethorphan with chlorpromazine. Int J Clin Pharmacol Ther Toxicol. 1990;28(4):147–52.PubMed
193.
Rosen MI, McMahon TJ, Woods SW, Pearsall HR, Kosten TR. A pilot study of dextromethorphan in naloxone-precipitated opiate withdrawal. Eur J Pharmacol. 1996;307(3):251–7.PubMed
194.
Bisaga A, Gianelli P, Popik P. Opiate withdrawal with dextromethorphan. Am J Psychiatry. 1997;154(4):584.PubMed
195.
Akerele E, Bisaga A, Sullivan MA, Garawi F, Comer SD, Thomas AA, et al. Dextromethorphan and quinidine combination for heroin detoxification. Am J Addict. 2008;17(3):176–80.
196.
Malek A, Amiri S, Habibi Asl B. The therapeutic effect of adding dextromethorphan to clonidine for reducing symptoms of opioid withdrawal: a randomized clinical trial. Int Sch Res Not. 2013;2013:1–5.
197.
Lin SK, Pan CH, Chen CH. A double-blind, placebo-controlled trial of dextromethorphan combined with clonidine in the treatment of heroin withdrawal. J Clin Psychopharmacol. 2014;34(4):508–12.PubMed
198.
Grace RF, Power I, Umedaly H, Zammit A, Mersiades M, Cousins MJ, et al. Preoperative dextromethorphan reduces intraoperative but not postoperative morphine requirements after laparotomy. Anesth Analg. 1998;87(5):1135–8.PubMed
199.
Weinbroum A, Lalayev G, Yashar T, Ben-Abraham R, Niv D, Flaishon R. Combined pre-incisional oral dextromethorphan and epidural lidocaine for postoperative pain reduction and morphine sparing: a randomised double-blind study on day-surgery patients. Anaesthesia. 2001;56(7):616–22.PubMed
200.
Weinbroum AA, Gorodetzky A, Nirkin A, Kollender Y, Bickels J, Marouani N, et al. Dextromethorphan for the reduction of immediate and late postoperative pain and morphine consumption in orthopedic oncology patients. Cancer. 2002;95(5):1164–70.PubMed
201.
McConaghy P, McSorley P, McCaughey W, Campbell W. Dextromethorphan and pain after total abdominal hysterectomy. Br J Anaesth. 1998;81(5):731–6.PubMed
202.
Rose JB, Cuy R, Cohen DE, Schreiner MS. Preoperative oral dextromethorphan does not reduce pain or analgesic consumption in children after adenotonsillectomy. Anesth Analg. 1999;88(4):749–53.PubMed
203.
Compton PA, Ling W, Torrington MA. CLINICAL STUDY: Lack of effect of chronic dextromethorphan on experimental pain tolerance in methadone-maintained patients. Addict Biol. 2008;13(3–4):393–402.PubMedCentralPubMed
204.
Taniguchi K, Shinjo K, Mizutani M, Shimada K, Ishikawa T, Menniti FS, et al. Antinociceptive activity of CP-101,606, an NMDA receptor NR2B subunit antagonist. Br J Pharmacol. 1997;122(5):809–12.PubMedCentralPubMed
205.
Nishimura W, Muratani T, Tatsumi S, Sakimura K, Mishina M, Minami T, et al. Characterization of N-methyl-d-aspartate receptor subunits responsible for postoperative pain. Eur J Pharmacol. 2004;503(1–3):71–5.PubMed
206.
Boyce S, Wyatt A, Webb J, O’donnell R, Mason G, Rigby M, et al. Selective NMDA NR2B antagonists induce antinociception without motor dysfunction: correlation with restricted localisation of NR2B subunit in dorsal horn. Neuropharmacology. 1999;38(5):611–23.PubMed
207.
Taylor CP, Angelotti T, Fauman E. Pharmacology and mechanism of action of pregabalin: the calcium channel alpha2-delta (alpha2-delta) subunit as a target for antiepileptic drug discovery. Epilepsy Res. 2007;73(2):137–50.PubMed
208.
Tassone DM, Boyce E, Guyer J, Nuzum D. Pregabalin: a novel gamma-aminobutyric acid analogue in the treatment of neuropathic pain, partial-onset seizures, and anxiety disorders. Clin Ther. 2007;29(1):26–48.PubMed
209.
Rose M, Kam P. Gabapentin: pharmacology and its use in pain management. Anaesthesia. 2002;57(5):451–62.PubMed
210.
Liang D-Y, Shi X, Li X, Li J, Clark JD. The β2 adrenergic receptor regulates morphine tolerance and physical dependence. Behav Brain Res. 2007;181(1):118–26.PubMedCentralPubMed
211.
212.
Hathway GJ, Vega-Avelaira D, Moss A, Ingram R, Fitzgerald M. Brief, low frequency stimulation of rat peripheral C-fibres evokes prolonged microglial-induced central sensitization in adults but not in neonates. Pain. 2009;144(1–2):110–8.PubMedCentralPubMed
213.
Hutchinson MR, Northcutt AL, Chao LW, Kearney JJ, Zhang Y, Berkelhammer DL, et al. Minocycline suppresses morphine-induced respiratory depression, suppresses morphine-induced reward, and enhances systemic morphine-induced analgesia. Brain Behav Immun. 2008;22(8):1248–56.PubMedCentralPubMed
214.
Hutchinson MR, Lewis SS, Coats BD, Skyba DA, Crysdale NY, Berkelhammer DL, et al. Reduction of opioid withdrawal and potentiation of acute opioid analgesia by systemic AV411 (ibudilast). Brain Behav Immun. 2009;23(2):240–50.
215.
Hama AT, Broadhead A, Lorrain DS, Sagen J. The antinociceptive effect of the asthma drug ibudilast in rat models of peripheral and central neuropathic pain. J Neurotrauma. 2012;29(3):600–10.PubMed
216.
Ellis A, Wieseler J, Favret J, Johnson KW, Rice KC, Maier SF, et al. Systemic administration of propentofylline, ibudilast, and (+)-naltrexone each reverses mechanical allodynia in a novel rat model of central neuropathic pain. J Pain. 2014;15(4):407–21.PubMedCentralPubMed
217.
Rolan P, Hutchinson M, Johnson K. Ibudilast: a review of its pharmacology, efficacy and safety in respiratory and neurological disease. Expert Opin Pharmacother. 2009;10(17):2897–904.PubMed
218.
Rolan P, Gibbons JA, He L, Chang E, Jones D, Gross MI, et al. Ibudilast in healthy volunteers: safety, tolerability and pharmacokinetics with single and multiple doses. Br J Clin Pharmacol. 2008;66(6):792–801.PubMedCentralPubMed
219.
Kim H-S, Suh Y-H. Minocycline and neurodegenerative diseases. Behav Brain Res. 2009;196(2):168–79.PubMed
220.
Sumracki NM, Hutchinson MR, Gentgall M, Briggs N, Williams DB, Rolan P. The effects of pregabalin and the glial attenuator minocycline on the response to intradermal capsaicin in patients with unilateral sciatica. PloS One. 2012;7(6):e38525.PubMedCentralPubMed
221.
Popiolek-Barczyk K, Rojewska E, Jurga AM, Makuch W, Zador F, Borsodi A, et al. Minocycline enhances the effectiveness of nociceptin/orphanin FQ during neuropathic pain. BioMed Res Int. 2014;2014:762930.PubMedCentralPubMed
222.
Ledeboer A, Sloane EM, Milligan ED, Frank MG, Mahony JH, Maier SF, et al. Minocycline attenuates mechanical allodynia and proinflammatory cytokine expression in rat models of pain facilitation. Pain. 2005;115(1):71–83.PubMed
223.
Li W-W, Setzu A, Zhao C, Franklin RJ. Minocycline-mediated inhibition of microglia activation impairs oligodendrocyte progenitor cell responses and remyelination in a non-immune model of demyelination. J Neuroimmunol. 2005;158(1):58–66.PubMed
224.
Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature. 1990;346(6284):561–4.PubMed
225.
Munro S, Thomas KL, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature. 1993;365(6441):61–5.PubMed
226.
Attal N, Brasseur L, Guirimand D, Clermond-Gnamien S, Atlami S, Bouhassira D. Are oral cannabinoids safe and effective in refractory neuropathic pain? Eur J Pain (Lond, Engl). 2004;8(2):173–7.
227.
Wallace M, Schulteis G, Atkinson JH, Wolfson T, Lazzaretto D, Bentley H, et al. Dose-dependent effects of smoked cannabis on capsaicin-induced pain and hyperalgesia in healthy volunteers. Anesthesiology. 2007;107(5):785–96.PubMed
228.
Buggy DJ, Toogood L, Maric S, Sharpe P, Lambert DG, Rowbotham DJ. Lack of analgesic efficacy of oral Δ-9-tetrahydrocannabinol in postoperative pain. Pain. 2003;106(1):169–72.PubMed
229.
Beaulieu P. Effects of nabilone, a synthetic cannabinoid, on postoperative pain. Canadian journal of anaesthesia =. Journal canadien d’anesthesie. 2006;53(8):769–75.PubMed
230.
Kraft B, Frickey NA, Kaufmann RM, Reif M, Frey R, Gustorff B, et al. Lack of analgesia by oral standardized cannabis extract on acute inflammatory pain and hyperalgesia in volunteers. Anesthesiology. 2008;109(1):101–10.PubMed
231.
Redmond WJ, Goffaux P, Potvin S, Marchand S. Analgesic and antihyperalgesic effects of nabilone on experimental heat pain. Curr Med Res Opinion. 2008;24(4):1017–24.
232.
Blake D, Robson P, Ho M, Jubb R, McCabe C. Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatology. 2006;45(1):50–2.PubMed
233.
Narang S, Gibson D, Wasan AD, Ross EL, Michna E, Nedeljkovic SS, et al. Efficacy of dronabinol as an adjuvant treatment for chronic pain patients on opioid therapy. J Pain. 2008;9(3):254–64.PubMed
234.
Notcutt W, Price M, Miller R, Newport S, Phillips C, Simmons S, et al. Initial experiences with medicinal extracts of cannabis for chronic pain: results from 34 ‘N of 1’studies. Anaesthesia. 2004;59(5):440–52.PubMed
235.
Svendsen KB, Jensen TS, Bach FW. Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial. BMJ. 2004;329(7460):253.PubMedCentralPubMed
236.
Wade DT, Robson P, House H, Makela P, Aram J. A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Clin Rehabil. 2003;17(1):21–9.PubMed
237.
Abrams DI, Jay CA, Shade SB, Vizoso H, Reda H, Press S, et al. Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology. 2007;68(7):515–21.PubMed
238.
Karst M, Salim K, Burstein S, Conrad I, Hoy L, Schneider U. Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain: a randomized controlled trial. JAMA. 2003;290(13):1757–62.PubMed
239.
Holdcroft A, Maze M, Dore C, Tebbs S, Thompson S. A multicenter dose-escalation study of the analgesic and adverse effects of an oral cannabis extract (Cannador) for postoperative pain management. Anesthesiology. 2006;104(5):1040–6.PubMed
240.
Skrabek RQ, Galimova L, Ethans K, Perry D. Nabilone for the treatment of pain in fibromyalgia. J Pain. 2008;9(2):164–73.PubMed
241.
Ellis RJ, Toperoff W, Vaida F, Van Den Brande G, Gonzales J, Gouaux B, et al. Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology. 2008;34(3):672–80.PubMedCentralPubMed
242.
Berman JS, Symonds C, Birch R. Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial. Pain. 2004;112(3):299–306.PubMed
243.
Eisenberg E, Ogintz M, Almog S. The Pharmacokinetics, efficacy, safety, and ease of use of a novel portable metered-dose cannabis inhaler in patients with chronic neuropathic pain: a phase 1a study. J Pain Palliat Care Pharmacother. 2014;28(3):216–25.PubMed
244.
de Vries M, van Rijckevorsel DC, Wilder-Smith OH, van Goor H. Dronabinol and chronic pain: importance of mechanistic considerations. Expert Opin Pharmacother. 2014;15(11):1–10.
245.
Martin WJ, Patrick SL, Coffin PO, Tsou K, Walker JM. An examination of the central sites of action of cannabinoid-induced antinociception in the rat. Life Sci. 1995;56(23):2103–9.PubMed
246.
Naef M, Curatolo M, Petersen-Felix S, Arendt-Nielsen L, Zbinden A, Brenneisen R. The analgesic effect of oral delta-9-tetrahydrocannabinol (THC), morphine, and a THC-morphine combination in healthy subjects under experimental pain conditions. Pain. 2003;105(1–2):79–88.PubMed
247.
Seeling W, Kneer L, Büchele B, Gschwend J, Maier L, Nett C, et al. Delta (9)-tetrahydrocannabinol and the opioid receptor agonist piritramide do not act synergistically in postoperative pain. Der Anaesthesist. 2006;55(4):391–400.PubMed
248.
Majewska MD. Neurosteroids: endogenous bimodal modulators of the GABAA receptor mechanism of action and physiological significance. Prog Neurobiol. 1992;38(4):379–94.PubMed
249.
Belelli D, Lambert JJ. Neurosteroids: endogenous regulators of the GABA(A) receptor. Nat Rev Neurosci. 2005;6(7):565–75.PubMed
250.
Mitchell EA, Gentet LJ, Dempster J, Belelli D. GABAA and glycine receptor-mediated transmission in rat lamina II neurones: relevance to the analgesic actions of neuroactive steroids. J Physiol. 2007;583(3):1021–40.PubMedCentralPubMed
251.
Poisbeau P, Keller AF, Aouad M, Kamoun N, Groyer G, Schumacher M. Analgesic strategies aimed at stimulating the endogenous production of allopregnanolone. Front Cell Neurosci. 2014;8:174.PubMedCentralPubMed
252.
Cashin MF, Moravek V. The physiological action of cholesterol. Am J Physiol Leg Content. 1927;82(2):294–8.
253.
Selye H. Anesthetic effect of steroid hormones. Exp Biol Med. 1941;46(1):116–21.
254.
Selye H, Masson G. Additional steroids with luteoid activity. Science. 1942;358(96):2494.
255.
Pathirathna S, Brimelow BC, Jagodic MM, Krishnan K, Jiang X, Zorumski CF, et al. New evidence that both T-type calcium channels and GABAA channels are responsible for the potent peripheral analgesic effects of 5alpha-reduced neuroactive steroids. Pain. 2005;114(3):429–43.PubMed
256.
Kavaliers M, Wiebe JP. Analgesic effects of the progesterone metabolite, 3α-hydroxy-5α-pregnan-20-one, and possible modes of action in mice. Brain Res. 1987;415(2):393–8.PubMed
257.
Frye CA, Duncan JE. Progesterone metabolites, effective at the GABAA receptor complex, attenuate pain sensitivity in rats. Brain Res. 1994;643(1):194–203.PubMed
258.
Frye CA, Rhodes ME, Walf A, Harney JP. Testosterone enhances aggression of wild-type mice but not those deficient in type I 5α-reductase. Brain Res. 2002;948(1):165–70.PubMed
259.
Frye CA, Walf AA, Rhodes ME, Harney JP. Progesterone enhances motor, anxiolytic, analgesic, and antidepressive behavior of wild-type mice, but not those deficient in type 1 5α-reductase. Brain Res. 2004;1004(1):116–24.PubMed
260.
Pednekar JR, Mulgaonker VK. Role of testosterone on pain threshold in rats. Indian J Physiol Pharmacol. 1995;39(4):423–4.PubMed
261.
Erden V, Yangn Z, Erkalp K, Delatioglu H, Bahçeci F, Seyhan A. Increased progesterone production during the luteal phase of menstruation may decrease anesthetic requirement. Anesth Analg. 2005;101(4):1007–11.PubMed
262.
Lee J, Lee J, Ko S. The relationship between serum progesterone concentration and anesthetic and analgesic requirements: a prospective observational study of parturients undergoing cesarean delivery. Anesth Analg. 2014;119(4):901–5.PubMed
263.
Gudin JA, Mogali S, Jones JD, Comer SD. Risks, management, and monitoring of combination opioid, benzodiazepines, and/or alcohol use. Postgrad Med. 2013;125(4):115–30.PubMedCentralPubMed
264.
Krishnan S, Salter A, Sullivan T, Gentgall M, White J, Rolan P. Comparison of pain models to detect opioid-induced hyperalgesia. J Pain Res. 2012;5:99.PubMedCentralPubMed
265.
Mogil JS, Wilson SG, Bon K, Eun Lee S, Chung K, Raber P, et al. Heritability of nociception I: responses of 11 inbred mouse strains on 12 measures of nociception. Pain. 1999;80(1):67–82.PubMed
266.
Mogil JS, Wilson SG, Bon K, Eun Lee S, Chung K, Raber P, et al. Heritability of nociception II.Types’ of nociception revealed by genetic correlation analysis. Pain. 1999;80(1):83–93.PubMed
267.
Liang DY, Liao G, Lighthall GK, Peltz G, Clark DJ. Genetic variants of the P-glycoprotein gene Abcb1b modulate opioid-induced hyperalgesia, tolerance and dependence. Pharmacogenet Genomics. 2006;16(11):825–35.PubMed
268.
Liang DY, Liao G, Wang J, Usuka J, Guo Y, Peltz G, et al. A genetic analysis of opioid-induced hyperalgesia in mice. Anesthesiology. 2006;104(5):1054–62.PubMedCentralPubMed
269.
Liang DY, Li X, Clark JD. Epigenetic regulation of opioid-induced hyperalgesia, dependence, and tolerance in mice. J Pain. 2013;14(1):36–47.PubMedCentralPubMed
270.
Doehring A, Oertel BG, Sittl R, Lötsch J. Chronic opioid use is associated with increased DNA methylation correlating with increased clinical pain. PAIN®. 2013;154(1):15–23.
Metadata
Title
Targeting Opioid-Induced Hyperalgesia in Clinical Treatment: Neurobiological Considerations
Authors
Caroline A. Arout
Ellen Edens
Ismene L. Petrakis
Mehmet Sofuoglu
Publication date
01-06-2015
Publisher
Springer International Publishing
Published in
CNS Drugs / Issue 6/2015
Print ISSN: 1172-7047
Electronic ISSN: 1179-1934
DOI
https://doi.org/10.1007/s40263-015-0255-x

Other articles of this Issue 6/2015

CNS Drugs 6/2015 Go to the issue

Current Opinion

Defining the Role of the Monoamine Oxidase-B Inhibitors for Parkinson’s Disease

Adis Drug Evaluation

Oxycodone/Naloxone PR: A Review in Severe Refractory Restless Legs Syndrome

Current Opinion

Targeting CGRP: A New Era for Migraine Treatment

Review Article

Alzheimer’s Disease: Lessons Learned from Amyloidocentric Clinical Trials

Original Research Article

Platform Therapy Compared with Natalizumab for Multiple Sclerosis: Relapse Rates and Time to Relapse Among Propensity Score-Matched US Patients

Leading Article

Developing Medications Targeting Glutamatergic Dysfunction in Autism: Progress to Date