Top

Molecular Pain

Published in:

Open Access 01-12-2014 | Research

TRPV1 antagonist attenuates postoperative hypersensitivity by central and peripheral mechanisms

Authors: Eva Uchytilova, Diana Spicarova, Jiri Palecek

Published in: Molecular Pain | Issue 1/2014

Abstract

Background

Acute postoperative pain is one of the frequent reasons for pain treatment. However, the exact mechanisms of its development are still not completely clear. Transient receptor potential vanilloid 1 (TRPV1) receptors are involved in nociceptive signaling in various hypersensitive states. Here we have investigated the contribution of TRPV1 receptors expressed on cutaneous peripheral nociceptive fibers and in the spinal cord on the development and maintenance of hypersensitivity to thermal and mechanical stimuli following surgical incision. A rat plantar incision model was used to test paw withdrawal responses to thermal and mechanical stimuli. The effect of the TRPV1 receptor antagonist SB366791 was investigated 1) by intrathecal injection 15 min before incision and 2) intradermal injection before (30 min) and immediately after the surgery. Vehicle-injected rats and naïve animals treated identically were used as controls.

Results

Plantar incision induced mechanical allodynia and hyperalgesia and thermal hyperalgesia. A single intrathecal administration of SB366791 significantly reduced postincisional thermal hyperalgesia and also attenuated mechanical allodynia, while mechanical hyperalgesia remained unaffected. Local intradermal SB366791 treatment reduced thermal hyperalgesia and mechanical allodynia without affecting mechanical hyperalgesia.

Conclusions

Our experiments suggest that both peripheral and spinal cord TRPV1 receptors are involved in increased cutaneous sensitivity following surgical incision. The analgesic effect of the TRPV1 receptor antagonist was especially evident in the reduction of thermal hyperalgesia. The activation of TRPV1 receptors represents an important mechanism in the development of postoperative hypersensitivity.

Available only for authorised users

Meyer RA: Cutaneous hyperalgesia and primary afferent sensitization. Pulm Pharmacol 1995, 8: 187–193. 10.1006/pulp.1995.1025PubMedCrossRef

Woolf CJ, Chong MS: Preemptive analgesia–treating postoperative pain by preventing the establishment of central sensitization. Anesth Analg 1993, 77: 362–379. 10.1213/00000539-199377020-00026PubMedCrossRef

Vandermeulen EP, Brennan TJ: Alterations in ascending dorsal horn neurons by a surgical incision in the rat foot. Anesthesiology 2000, 93: discussion 1296A-discussion 1302A.CrossRef

Nagakura Y, Jones TL, Malkmus SA, Sorkin L, Yaksh TL: The sensitization of a broad spectrum of sensory nerve fibers in a rat model of acute postoperative pain and its response to intrathecal pharmacotherapy. Pain 2008, 139: 569–577. 10.1016/j.pain.2008.06.014PubMedCentralPubMedCrossRef

Jones TL, Lustig AC, Sorkin LS: Secondary hyperalgesia in the postoperative pain model is dependent on spinal calcium/calmodulin-dependent protein kinase II alpha activation. Anesth Analg 2007, 105: 1650–1656. table of contents 10.1213/01.ane.0000287644.00420.49PubMedCrossRef

Brennan TJ, Vandermeulen EP, Gebhart GF: Characterization of a rat model of incisional pain. Pain 1996, 64: 493–501. 10.1016/0304-3959(95)01441-1PubMedCrossRef

Pogatzki EM, Gebhart GF, Brennan TJ: Characterization of Adelta- and C-fibers innervating the plantar rat hindpaw one day after an incision. J Neurophysiol 2002, 87: 721–731.PubMed

Carreira EU, Carregaro V, Teixeira MM, Moriconi A, Aramini A, Verri WA Jr, Ferreira SH, Cunha FQ, Cunha TM: Neutrophils recruited by CXCR1/2 signalling mediate post-incisional pain. Eur J Pain 2013, 17: 654–663. 10.1002/j.1532-2149.2012.00240.xPubMedCrossRef

Woo YC, Park SS, Subieta AR, Brennan TJ: Changes in tissue pH and temperature after incision indicate acidosis may contribute to postoperative pain. Anesthesiology 2004, 101: 468–475. 10.1097/00000542-200408000-00029PubMedCrossRef

10.

Banik RK, Subieta AR, Wu C, Brennan TJ: Increased nerve growth factor after rat plantar incision contributes to guarding behavior and heat hyperalgesia. Pain 2005, 117: 68–76. 10.1016/j.pain.2005.05.017PubMedCrossRef

11.

Wu C, Boustany L, Liang H, Brennan TJ: Nerve growth factor expression after plantar incision in the rat. Anesthesiology 2007, 107: 128–135. 10.1097/01.anes.0000267512.08619.bdPubMedCrossRef

12.

Omote K, Kawamata T, Nakayama Y, Kawamata M, Hazama K, Namiki A: The effects of peripheral administration of a novel selective antagonist for prostaglandin E receptor subtype EP(1), ONO-8711, in a rat model of postoperative pain. Anesth Analg 2001, 92: 233–238.PubMedCrossRef

13.

Furedi R, Bolcskei K, Szolcsanyi J, Petho G: Comparison of the peripheral mediator background of heat injury- and plantar incision-induced drop of the noxious heat threshold in the rat. Life Sci 2010, 86: 244–250. 10.1016/j.lfs.2009.12.010PubMedCrossRef

14.

Miura M, Sasaki M, Mizukoshi K, Shibasaki M, Izumi Y, Shimosato G, Amaya F: Peripheral sensitization caused by insulin-like growth factor 1 contributes to pain hypersensitivity after tissue injury. Pain 2011, 152: 888–895. 10.1016/j.pain.2011.01.004PubMedCrossRef

15.

Deval E, Noel J, Gasull X, Delaunay A, Alloui A, Friend V, Eschalier A, Lazdunski M, Lingueglia E: Acid-sensing ion channels in postoperative pain. J Neurosci 2011, 31: 6059–6066. 10.1523/JNEUROSCI.5266-10.2011PubMedCrossRef

16.

Tillu DV, Melemedjian OK, Asiedu MN, Qu N, De Felice M, Dussor G, Price TJ: Resveratrol engages AMPK to attenuate ERK and mTOR signaling in sensory neurons and inhibits incision-induced acute and chronic pain. Mol Pain 2012, 8: 5. 10.1186/1744-8069-8-5PubMedCentralPubMedCrossRef

17.

Kroin JS, Ling ZD, Buvanendran A, Tuman KJ: Upregulation of spinal cyclooxygenase-2 in rats after surgical incision. Anesthesiology 2004, 100: 364–369. 10.1097/00000542-200402000-00027PubMedCrossRef

18.

Zhu X, Conklin D, Eisenach JC: Cyclooxygenase-1 in the spinal cord plays an important role in postoperative pain. Pain 2003, 104: 15–23. 10.1016/S0304-3959(02)00465-7PubMedCrossRef

19.

Omote K, Yamamoto H, Kawamata T, Nakayama Y, Namiki A: The effects of intrathecal administration of an antagonist for prostaglandin E receptor subtype EP(1) on mechanical and thermal hyperalgesia in a rat model of postoperative pain. Anesth Analg 2002, 95: 1708–1712. table of contents 10.1097/00000539-200212000-00044PubMedCrossRef

20.

Li CQ, Xu JM, Liu D, Zhang JY, Dai RP: Brain derived neurotrophic factor (BDNF) contributes to the pain hypersensitivity following surgical incision in the rats. Mol Pain 2008, 4: 27. 10.1186/1744-8069-4-27PubMedCentralPubMedCrossRef

21.

Fu D, Guo Q, Ai Y, Cai H, Yan J, Dai R: Glial activation and segmental upregulation of interleukin-1beta (IL-1beta) in the rat spinal cord after surgical incision. Neurochem Res 2006, 31: 333–340. 10.1007/s11064-005-9032-4PubMedCrossRef

22.

Peters CM, Eisenach JC: Contribution of the chemokine (C-C motif) ligand 2 (CCL2) to mechanical hypersensitivity after surgical incision in rats. Anesthesiology 2010, 112: 1250–1258. 10.1097/ALN.0b013e3181d3d978PubMedCentralPubMedCrossRef

23.

Silveira JW, Dias QM, Del Bel EA, Prado WA: Serotonin receptors are involved in the spinal mediation of descending facilitation of surgical incision-induced increase of Fos-like immunoreactivity in rats. Mol Pain 2010, 6: 17. 10.1186/1744-8069-6-17PubMedCentralPubMedCrossRef

24.

Reichl S, Augustin M, Zahn PK, Pogatzki-Zahn EM: Peripheral and spinal GABAergic regulation of incisional pain in rats. Pain 2012, 153: 129–141. 10.1016/j.pain.2011.09.028PubMedCrossRef

25.

Wen YR, Suter MR, Ji RR, Yeh GC, Wu YS, Wang KC, Kohno T, Sun WZ, Wang CC: Activation of p38 mitogen-activated protein kinase in spinal microglia contributes to incision-induced mechanical allodynia. Anesthesiology 2009, 110: 155–165. 10.1097/ALN.0b013e318190bc16PubMedCrossRef

26.

Xu B, Guan XH, Yu JX, Lv J, Zhang HX, Fu QC, Xiang HB, Bu HL, Shi D, Shu B, Qin LS, Manyande A, Tian YK: Activation of spinal phosphatidylinositol 3-kinase/protein kinase B mediates pain behavior induced by plantar incision in mice. Exp Neurol 2014, 255: 71–82.PubMedCrossRef

27.

Caterina MJ, Julius D: The vanilloid receptor: a molecular gateway to the pain pathway. Annu Rev Neurosci 2001, 24: 487–517. 10.1146/annurev.neuro.24.1.487PubMedCrossRef

28.

Pogatzki-Zahn EM, Shimizu I, Caterina M, Raja SN: Heat hyperalgesia after incision requires TRPV1 and is distinct from pure inflammatory pain. Pain 2005, 115: 296–307. 10.1016/j.pain.2005.03.010PubMedCrossRef

29.

Banik RK, Brennan TJ: Trpv1 mediates spontaneous firing and heat sensitization of cutaneous primary afferents after plantar incision. Pain 2009, 141: 41–51. 10.1016/j.pain.2008.10.004PubMedCentralPubMedCrossRef

30.

Simone DA, Nolano M, Johnson T, Wendelschafer-Crabb G, Kennedy WR: Intradermal injection of capsaicin in humans produces degeneration and subsequent reinnervation of epidermal nerve fibers: correlation with sensory function. J Neurosci 1998, 18: 8947–8959.PubMed

31.

Jeffry JA, Yu SQ, Sikand P, Parihar A, Evans MS, Premkumar LS: Selective targeting of TRPV1 expressing sensory nerve terminals in the spinal cord for long lasting analgesia. PLoS One 2009, 4: e7021. 10.1371/journal.pone.0007021PubMedCentralPubMedCrossRef

32.

Pospisilova E, Palecek J: Post-operative pain behavior in rats is reduced after single high-concentration capsaicin application. Pain 2006, 125: 233–243. 10.1016/j.pain.2006.05.021PubMedCrossRef

33.

Kang S, Wu C, Banik RK, Brennan TJ: Effect of capsaicin treatment on nociceptors in rat glabrous skin one day after plantar incision. Pain 2010, 148: 128–140. 10.1016/j.pain.2009.10.031PubMedCentralPubMedCrossRef

34.

Aasvang EK, Hansen JB, Malmstrom J, Asmussen T, Gennevois D, Struys MM, Kehlet H: The effect of wound instillation of a novel purified capsaicin formulation on postherniotomy pain: a double-blind, randomized, placebo-controlled study. Anesth Analg 2008, 107: 282–291. 10.1213/ane.0b013e31816b94c9PubMedCrossRef

35.

Dahl JB, Mathiesen O, Kehlet H: An expert opinion on postoperative pain management, with special reference to new developments. Expert Opin Pharmacother 2010, 11: 2459–2470. 10.1517/14656566.2010.499124PubMedCrossRef

36.

Gavva NR: Body-temperature maintenance as the predominant function of the vanilloid receptor TRPV1. Trends Pharmacol Sci 2008, 29: 550–557. 10.1016/j.tips.2008.08.003PubMedCrossRef

37.

Gunthorpe MJ, Rami HK, Jerman JC, Smart D, Gill CH, Soffin EM, Luis Hannan S, Lappin SC, Egerton J, Smith GD, Worby A, Howett L, Owen D, Nasir S, Davies CH, Thompson M, Wyman PA, Randall AD, Davis JB: Identification and characterisation of SB-366791, a potent and selective vanilloid receptor (VR1/TRPV1) antagonist. Neuropharmacology 2004, 46: 133–149. 10.1016/S0028-3908(03)00305-8PubMedCrossRef

38.

Zahn PK, Brennan TJ: Incision-induced changes in receptive field properties of rat dorsal horn neurons. Anesthesiology 1999, 91: 772–785. 10.1097/00000542-199909000-00030PubMedCrossRef

39.

Whiteside GT, Harrison J, Boulet J, Mark L, Pearson M, Gottshall S, Walker K: Pharmacological characterisation of a rat model of incisional pain. Br J Pharmacol 2004, 141: 85–91. 10.1038/sj.bjp.0705568PubMedCentralPubMedCrossRef

40.

Barabas ME, Stucky CL: TRPV1, but not TRPA1, in primary sensory neurons contributes to cutaneous incision-mediated hypersensitivity. Mol Pain 2013, 9: 9. 10.1186/1744-8069-9-9PubMedCentralPubMedCrossRef

41.

Honore P, Chandran P, Hernandez G, Gauvin DM, Mikusa JP, Zhong C, Joshi SK, Ghilardi JR, Sevcik MA, Fryer RM, Segreti JA, Banfor PN, Marsh K, Neelands T, Bayburt E, Daanen JF, Gomtsyan A, Lee CH, Kort ME, Reilly RM, Surowy CS, Kym PR, Mantyh PW, Sullivan JP, Jarvis MF, Faltynek CR: Repeated dosing of ABT-102, a potent and selective TRPV1 antagonist, enhances TRPV1-mediated analgesic activity in rodents, but attenuates antagonist-induced hyperthermia. Pain 2009, 142: 27–35. 10.1016/j.pain.2008.11.004PubMedCrossRef

42.

Honore P, Wismer CT, Mikusa J, Zhu CZ, Zhong C, Gauvin DM, Gomtsyan A, El Kouhen R, Lee CH, Marsh K, Sullivan JP, Faltynek CR, Jarvis MF: A-425619 [1-isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)-urea], a novel transient receptor potential type V1 receptor antagonist, relieves pathophysiological pain associated with inflammation and tissue injury in rats. J Pharmacol Exp Ther 2005, 314: 410–421. 10.1124/jpet.105.083915PubMedCrossRef

43.

Wu C, Gavva NR, Brennan TJ: Effect of AMG0347, a transient receptor potential type V1 receptor antagonist, and morphine on pain behavior after plantar incision. Anesthesiology 2008, 108: 1100–1108. 10.1097/ALN.0b013e31817302b3PubMedCrossRef

44.

Tekus V, Bolcskei K, Kis-Varga A, Dezsi L, Szentirmay E, Visegrady A, Horvath C, Szolcsanyi J, Petho G: Effect of transient receptor potential vanilloid 1 (TRPV1) receptor antagonist compounds SB705498, BCTC and AMG9810 in rat models of thermal hyperalgesia measured with an increasing-temperature water bath. Eur J Pharmacol 2010, 641: 135–141. 10.1016/j.ejphar.2010.05.052PubMedCrossRef

45.

Spicarova D, Palecek J: The role of spinal cord vanilloid (TRPV1) receptors in pain modulation. Physiol Res 2008,57(Suppl 3):S69-S77.PubMed

46.

Spicarova D, Nerandzic V, Palecek J: Update on the role of spinal cord TRPV1 receptors in pain modulation. Physiol Res 2014,63(Suppl 1):S225-S236.PubMed

47.

Lappin SC, Randall AD, Gunthorpe MJ, Morisset V: TRPV1 antagonist, SB-366791, inhibits glutamatergic synaptic transmission in rat spinal dorsal horn following peripheral inflammation. Eur J Pharmacol 2006, 540: 73–81. 10.1016/j.ejphar.2006.04.046PubMedCrossRef

48.

Spicarova D, Palecek J: The role of the TRPV1 endogenous agonist N-Oleoyldopamine in modulation of nociceptive signaling at the spinal cord level. J Neurophysiol 2009, 102: 234–243. 10.1152/jn.00024.2009PubMedCrossRef

49.

Park CK, Lu N, Xu ZZ, Liu T, Serhan CN, Ji RR: Resolving TRPV1- and TNF-alpha-mediated spinal cord synaptic plasticity and inflammatory pain with neuroprotectin D1. J Neurosci 2011, 31: 15072–15085. 10.1523/JNEUROSCI.2443-11.2011PubMedCentralPubMedCrossRef

50.

Spofford CM, Brennan TJ: Gene expression in skin, muscle, and dorsal root ganglion after plantar incision in the rat. Anesthesiology 2012, 117: 161–172. 10.1097/ALN.0b013e31825a2a2bPubMedCentralPubMedCrossRef

51.

Chuang HH, Prescott ED, Kong H, Shields S, Jordt SE, Basbaum AI, Chao MV, Julius D: Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition. Nature 2001, 411: 957–962. 10.1038/35082088PubMedCrossRef

52.

Zhang X, Huang J, McNaughton PA: NGF rapidly increases membrane expression of TRPV1 heat-gated ion channels. EMBO J 2005, 24: 4211–4223. 10.1038/sj.emboj.7600893PubMedCentralPubMedCrossRef

53.

Schmutzler BS, Roy S, Hingtgen CM: Glial cell line-derived neurotrophic factor family ligands enhance capsaicin-stimulated release of calcitonin gene-related peptide from sensory neurons. Neuroscience 2009, 161: 148–156. 10.1016/j.neuroscience.2009.03.006PubMedCentralPubMedCrossRef

54.

Malin SA, Molliver DC, Koerber HR, Cornuet P, Frye R, Albers KM, Davis BM: Glial cell line-derived neurotrophic factor family members sensitize nociceptors in vitro and produce thermal hyperalgesia in vivo. J Neurosci 2006, 26: 8588–8599. 10.1523/JNEUROSCI.1726-06.2006PubMedCrossRef

55.

Elitt CM, McIlwrath SL, Lawson JJ, Malin SA, Molliver DC, Cornuet PK, Koerber HR, Davis BM, Albers KM: Artemin overexpression in skin enhances expression of TRPV1 and TRPA1 in cutaneous sensory neurons and leads to behavioral sensitivity to heat and cold. J Neurosci 2006, 26: 8578–8587. 10.1523/JNEUROSCI.2185-06.2006PubMedCrossRef

56.

Andratsch M, Mair N, Constantin CE, Scherbakov N, Benetti C, Quarta S, Vogl C, Sailer CA, Uceyler N, Brockhaus J, Martini R, Sommer C, Zeilhofer HU, Muller W, Kuner R, Davis JB, Rose-John S, Kress M: A key role for gp130 expressed on peripheral sensory nerves in pathological pain. J Neurosci 2009, 29: 13473–13483. 10.1523/JNEUROSCI.1822-09.2009PubMedCrossRef

57.

Furedi R, Bolcskei K, Szolcsanyi J, Petho G: Effects of analgesics on the plantar incision-induced drop of the noxious heat threshold measured with an increasing-temperature water bath in the rat. Eur J Pharmacol 2009, 605: 63–67. 10.1016/j.ejphar.2008.12.035PubMedCrossRef

58.

Sugiura T, Tominaga M, Katsuya H, Mizumura K: Bradykinin lowers the threshold temperature for heat activation of vanilloid receptor 1. J Neurophysiol 2002, 88: 544–548.PubMed

59.

Moriyama T, Higashi T, Togashi K, Iida T, Segi E, Sugimoto Y, Tominaga T, Narumiya S, Tominaga M: Sensitization of TRPV1 by EP1 and IP reveals peripheral nociceptive mechanism of prostaglandins. Mol Pain 2005, 1: 3. 10.1186/1744-8069-1-3PubMedCentralPubMedCrossRef

60.

Tominaga M, Wada M, Masu M: Potentiation of capsaicin receptor activity by metabotropic ATP receptors as a possible mechanism for ATP-evoked pain and hyperalgesia. Proc Natl Acad Sci U S A 2001, 98: 6951–6956. 10.1073/pnas.111025298PubMedCentralPubMedCrossRef

61.

Yoshida T, Inoue R, Morii T, Takahashi N, Yamamoto S, Hara Y, Tominaga M, Shimizu S, Sato Y, Mori Y: Nitric oxide activates TRP channels by cysteine S-nitrosylation. Nat Chem Biol 2006, 2: 596–607. 10.1038/nchembio821PubMedCrossRef

62.

Dolan S, Kelly JG, Huan M, Nolan AM: Transient up-regulation of spinal cyclooxygenase-2 and neuronal nitric oxide synthase following surgical inflammation. Anesthesiology 2003, 98: 170–180. 10.1097/00000542-200301000-00027PubMedCrossRef

63.

Spicarova D, Adamek P, Kalynovska N, Mrozkova P, Palecek J: TRPV1 receptor inhibition decreases CCL2-induced hyperalgesia. Neuropharmacology 2014, 81: 75–84.PubMedCrossRef

64.

Ferreira J, Triches KM, Medeiros R, Calixto JB: Mechanisms involved in the nociception produced by peripheral protein kinase c activation in mice. Pain 2005, 117: 171–181. 10.1016/j.pain.2005.06.001PubMedCrossRef

65.

Claudino RF, Kassuya CA, Ferreira J, Calixto JB: Pharmacological and molecular characterization of the mechanisms involved in prostaglandin E2-induced mouse paw edema. J Pharmacol Exp Ther 2006, 318: 611–618. 10.1124/jpet.106.102806PubMedCrossRef

66.

Castro-Junior CJ, Milano J, Souza AH, Silva JF, Rigo FK, Dalmolin G, Cordeiro MN, Richardson M, Barros AG, Gomez RS, Silva MA, Kushmerick C, Ferreira J, Gomez MV: Phalpha1beta toxin prevents capsaicin-induced nociceptive behavior and mechanical hypersensitivity without acting on TRPV1 channels. Neuropharmacology 2013, 71: 237–246.PubMedCrossRef

67.

Russell FA, Fernandes ES, Courade JP, Keeble JE, Brain SD: Tumour necrosis factor alpha mediates transient receptor potential vanilloid 1-dependent bilateral thermal hyperalgesia with distinct peripheral roles of interleukin-1beta, protein kinase C and cyclooxygenase-2 signalling. Pain 2009, 142: 264–274. 10.1016/j.pain.2009.01.021PubMedCrossRef

Title: TRPV1 antagonist attenuates postoperative hypersensitivity by central and peripheral mechanisms
Authors: Eva Uchytilova
Diana Spicarova
Jiri Palecek
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Molecular Pain / Issue 1/2014
Electronic ISSN: 1744-8069
DOI: https://doi.org/10.1186/1744-8069-10-67

Keynote webinar | Spotlight on medication adherence

Springer Medicine

TRPV1 antagonist attenuates postoperative hypersensitivity by central and peripheral mechanisms

Abstract

Background

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2014

No association of polymorphisms in the serotonin transporter gene with thermal pain sensation in healthy individuals

Spatial and temporal pattern of changes in the number of GAD65-immunoreactive inhibitory terminals in the rat superficial dorsal horn following peripheral nerve injury

Roles of ASIC3, TRPV1, and NaV1.8 in the transition from acute to chronic pain in a mouse model of fibromyalgia

Anoctamin 1 contributes to inflammatory and nerve-injury induced hypersensitivity

Sphingosine 1-phosphate to p38 signaling via S1P1 receptor and Gαi/o evokes augmentation of capsaicin-induced ionic currents in mouse sensory neurons

Loss of long-term depression in the insular cortex after tail amputation in adult mice