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Published in: Techniques in Coloproctology 3/2009

01-09-2009 | Original Article

Randomized placebo-controlled trial on local applications of opioids after hemorrhoidectomy

Authors: G. Tegon, L. Pulzato, L. Passarella, D. Guidolin, M. Zusso, P. Giusti

Published in: Techniques in Coloproctology | Issue 3/2009

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Abstract

Background

Hemorrhoidectomy is associated with considerable postoperative pain. This study assessed whether a small dose of morphine or oxycodone administered in the embedded sponge set in the anus at the end of a hemorrhoidectomy intervention reduced postoperative pain.

Methods

The presence of opioid receptors was assessed in the anal mucosa excised from ten patients with perianal condyloma acuminata and 19 patients with symptomatic third–fourth degree hemorrhoids. A double-blind prospective randomized placebo-controlled trial was then conducted in 135 patients with hemorrhoids. Hemorrhoidectomy patients were randomized to morphine (MG), oxycodone (OG), or control (CG) groups, each patient having an absorbable sponge dressing left in the anus embedded with 1 mg of morphine, 1 mg oxycodone, or vehicle, respectively. The mean time for the first dose of analgesic drugs, the use of analgesics, and the mean time to void bladder was evaluated.

Results

The presence of κ- and δ-opioid receptor immunoreactivity was detected in the anal mucosa excised from patients with perianal condyloma acuminata and hemorrhoids. Furthermore, there was a significant (P < 0.001) upregulation of κ receptor immunoreactive-like material in hemorrhoidectomy patients. The mean time for the first analgesic administration was significantly increased (P < 0.001) in MG versus CG. A further significant increase (P < 0.001) was observed in the OG patient group. The mean time for voiding was significantly higher in CG when compared to the MG and OG patient groups.

Conclusion

The local administration of very low doses of κ-opioid agonist decreased hemorrhoidectomy postoperative pain through the interaction with specific opioid receptors located on anal mucosa.
Literature
1.
go back to reference Goligher J (1984) Surgery of the anus, rectum, and colon, 5th edn. Baillière Tindall, London Goligher J (1984) Surgery of the anus, rectum, and colon, 5th edn. Baillière Tindall, London
2.
go back to reference Roques BP, Noble F, Fournie-Zaluski M-C (1999) Endogenous opioid peptides and analgesia. In: Kein C (ed) Opioids in pain control: basic and clinical aspect. Cambridge University Press, London, pp 21–45 Roques BP, Noble F, Fournie-Zaluski M-C (1999) Endogenous opioid peptides and analgesia. In: Kein C (ed) Opioids in pain control: basic and clinical aspect. Cambridge University Press, London, pp 21–45
3.
go back to reference Stein C, Schafer M, Machelska H (2003) Attacking pain at its source: new perspectives on opioids. Nat Med 9:1003–1008PubMedCrossRef Stein C, Schafer M, Machelska H (2003) Attacking pain at its source: new perspectives on opioids. Nat Med 9:1003–1008PubMedCrossRef
4.
go back to reference Mestek A, Hurley JH, Bye LS et al (1995) The human mu opioid receptor: modulation of functional desensitization by calcium/calmodulin-dependent protein kinase and protein kinase. C J Neurosci 15(3 Pt 2):2396–2406 Mestek A, Hurley JH, Bye LS et al (1995) The human mu opioid receptor: modulation of functional desensitization by calcium/calmodulin-dependent protein kinase and protein kinase. C J Neurosci 15(3 Pt 2):2396–2406
5.
go back to reference Owens WD, Felts JA, Spitznagel EL Jr (1978) ASA Physical Status Classifications a study of consistency of ratings. Anaesthesiology 49:239–243CrossRef Owens WD, Felts JA, Spitznagel EL Jr (1978) ASA Physical Status Classifications a study of consistency of ratings. Anaesthesiology 49:239–243CrossRef
6.
go back to reference Holzer P (2004) Opioids and opioid receptors in the enteric nervous system: from a problem in opioid analgesia to a possible new prokinetic therapy in humans. Neurosci Lett 361:192–195PubMedCrossRef Holzer P (2004) Opioids and opioid receptors in the enteric nervous system: from a problem in opioid analgesia to a possible new prokinetic therapy in humans. Neurosci Lett 361:192–195PubMedCrossRef
7.
go back to reference Calignano A, Moncada S, Di Rosa M (1991) Endogenous nitric oxide modulates morphine-induced constipation. Biochem Biophys Res Commun 181:889–893PubMedCrossRef Calignano A, Moncada S, Di Rosa M (1991) Endogenous nitric oxide modulates morphine-induced constipation. Biochem Biophys Res Commun 181:889–893PubMedCrossRef
8.
go back to reference De Luca A, Coupar IM (1996) Insights into opioid action in the intestinal tract. Pharmacol Ther 69:103–115PubMedCrossRef De Luca A, Coupar IM (1996) Insights into opioid action in the intestinal tract. Pharmacol Ther 69:103–115PubMedCrossRef
9.
go back to reference Valle L, Pol O, Puig MM (2001) Intestinal inflammation enhances the inhibitory effects of opioids on intestinal permeability in mice. J Pharmacol Exp Ther 296:378–387PubMed Valle L, Pol O, Puig MM (2001) Intestinal inflammation enhances the inhibitory effects of opioids on intestinal permeability in mice. J Pharmacol Exp Ther 296:378–387PubMed
10.
go back to reference Bagnol D, Mansour A, Akil H, Watson SJ (1997) Cellular localization and distribution of the cloned mu and kappa opioid receptors in rat gastrointestinal tract. Neuroscience 81:579–591PubMedCrossRef Bagnol D, Mansour A, Akil H, Watson SJ (1997) Cellular localization and distribution of the cloned mu and kappa opioid receptors in rat gastrointestinal tract. Neuroscience 81:579–591PubMedCrossRef
11.
go back to reference Nano JL, Fournel S, Rampal P (2000) Characterization of delta-opioid receptors and effect of enkephalins on IRD 98 rat epithelial intestinal cell line. Pfugers Arch 439:547–554CrossRef Nano JL, Fournel S, Rampal P (2000) Characterization of delta-opioid receptors and effect of enkephalins on IRD 98 rat epithelial intestinal cell line. Pfugers Arch 439:547–554CrossRef
12.
go back to reference Franklin EJ, Seetharam S, Lowney J, Horgan PG (2003) Randomized, clinical trial of Ligasure vs conventional diathermy in hemorrhoidectomy. Dis Colon Rectum 46:1380–1383PubMedCrossRef Franklin EJ, Seetharam S, Lowney J, Horgan PG (2003) Randomized, clinical trial of Ligasure vs conventional diathermy in hemorrhoidectomy. Dis Colon Rectum 46:1380–1383PubMedCrossRef
13.
go back to reference Wasvary HJ, Hain J, Mosed-Vogel M, Bendick P, Barkel DC, Klein SN (2001) Randomized, prospective, double-blind, placebo-controlled trial of effect of nitroglycerine ointment on pain after hemorrhoidectomy. Dis Colon Rectum 44:1069–1073PubMedCrossRef Wasvary HJ, Hain J, Mosed-Vogel M, Bendick P, Barkel DC, Klein SN (2001) Randomized, prospective, double-blind, placebo-controlled trial of effect of nitroglycerine ointment on pain after hemorrhoidectomy. Dis Colon Rectum 44:1069–1073PubMedCrossRef
14.
go back to reference Kilbride M, Morse M, Senagore A (1994) Transdermal fentanyl improves management of postoperative hemorrhoidectomy pain. Dis Colon Rectum 37:1070–1072PubMedCrossRef Kilbride M, Morse M, Senagore A (1994) Transdermal fentanyl improves management of postoperative hemorrhoidectomy pain. Dis Colon Rectum 37:1070–1072PubMedCrossRef
15.
go back to reference Brunat G, Pouzeratte Y, Mann C, Didelot JM, Rochon JC, Eledjam JJ (2003) Posterior perineal block with ropivacaine 0.75% for pain control during and after hemorrhoidectomy. Reg Anesth Pain Med 28:228–232PubMed Brunat G, Pouzeratte Y, Mann C, Didelot JM, Rochon JC, Eledjam JJ (2003) Posterior perineal block with ropivacaine 0.75% for pain control during and after hemorrhoidectomy. Reg Anesth Pain Med 28:228–232PubMed
16.
go back to reference Davies J, Duffy D, Boyt N, Aghahoseini A, Alexander D, Leveson S (2003) Botulinum toxin (Botox) reduces pain after hemorrhoidectomy; results of double-blind, randomized study. Dis Colon Rectum 46:1097–1102PubMedCrossRef Davies J, Duffy D, Boyt N, Aghahoseini A, Alexander D, Leveson S (2003) Botulinum toxin (Botox) reduces pain after hemorrhoidectomy; results of double-blind, randomized study. Dis Colon Rectum 46:1097–1102PubMedCrossRef
17.
go back to reference Tan KY, Sng KK, Tay KH, Lai JH, Eu K (2006) Randomized clinical trial of 0.2 percent glyceryl trinitrate ointment for wound healing and pain reduction after diathermy hemorrhoidectomy. Br J Surg 93:1464–1468PubMedCrossRef Tan KY, Sng KK, Tay KH, Lai JH, Eu K (2006) Randomized clinical trial of 0.2 percent glyceryl trinitrate ointment for wound healing and pain reduction after diathermy hemorrhoidectomy. Br J Surg 93:1464–1468PubMedCrossRef
18.
go back to reference Nicholson TJ, Armstrong D (2004) Topical Metronidazole (10 percent) decreases posthemorrhoidectomy pain and improves healing. Dis Colon Rectum 47:711–716PubMedCrossRef Nicholson TJ, Armstrong D (2004) Topical Metronidazole (10 percent) decreases posthemorrhoidectomy pain and improves healing. Dis Colon Rectum 47:711–716PubMedCrossRef
19.
go back to reference Gupta PJ, Heda PS, Kalaskar S, Tamaskar VP (2008) Topical Sucralfate decrease pain after hemorrhoidectomy and improves healing: randomized, blinded, controlled study. Dis Colon Rectum 51:231–234PubMedCrossRef Gupta PJ, Heda PS, Kalaskar S, Tamaskar VP (2008) Topical Sucralfate decrease pain after hemorrhoidectomy and improves healing: randomized, blinded, controlled study. Dis Colon Rectum 51:231–234PubMedCrossRef
20.
go back to reference Vinson-Bonnet B, Coltat JC, Fingerhut A, Bonnet F (2002) Local infiltration with ropivacaine improves immediate postoperative pain control after hemorrhoidal surgery. Dis Colon Rectum 45:104–108PubMedCrossRef Vinson-Bonnet B, Coltat JC, Fingerhut A, Bonnet F (2002) Local infiltration with ropivacaine improves immediate postoperative pain control after hemorrhoidal surgery. Dis Colon Rectum 45:104–108PubMedCrossRef
21.
go back to reference Bourget JL, Clark J, Joy N (1999) Comparing preincisional with postincisional bupivacaine infiltration in the management of postoperative pain. Arch Surg 133:226 Bourget JL, Clark J, Joy N (1999) Comparing preincisional with postincisional bupivacaine infiltration in the management of postoperative pain. Arch Surg 133:226
22.
go back to reference Sengupta JN, Snider A, Su X, Gebhart GF (1999) Effects of kappa opioids in the inflamed rat colon. Pain 79:175–185PubMedCrossRef Sengupta JN, Snider A, Su X, Gebhart GF (1999) Effects of kappa opioids in the inflamed rat colon. Pain 79:175–185PubMedCrossRef
23.
go back to reference Poonyachoti S, Kulkarni-Narla A, Brown DR (2002) Chemical coding of neurons expressing delta- and kappa-opioid receptor and type I vanilloid receptor immunoreactivities in the porcine ileum. Cell Tissue Res 307:23–33PubMedCrossRef Poonyachoti S, Kulkarni-Narla A, Brown DR (2002) Chemical coding of neurons expressing delta- and kappa-opioid receptor and type I vanilloid receptor immunoreactivities in the porcine ileum. Cell Tissue Res 307:23–33PubMedCrossRef
24.
go back to reference Zaheer S, Reilly WT, Pemberton JH, Ilstrup D (1998) Urinary retention after operations for benign anorectal diseases. Dis Colon Rectum 41:696–704PubMedCrossRef Zaheer S, Reilly WT, Pemberton JH, Ilstrup D (1998) Urinary retention after operations for benign anorectal diseases. Dis Colon Rectum 41:696–704PubMedCrossRef
25.
go back to reference Bailey HR, Ferguson JA (1976) Prevention of urinary retention by fluid restriction following anorectal operations. Dis Colon Rectum 19:250–252PubMedCrossRef Bailey HR, Ferguson JA (1976) Prevention of urinary retention by fluid restriction following anorectal operations. Dis Colon Rectum 19:250–252PubMedCrossRef
26.
go back to reference Hoff SD, Bailey HR, Butts DR et al (1994) Ambulatory surgical hemorrhoidectomy—a solution to postoperative urinary retention? Dis Colon Rectum 37:1242–1244PubMedCrossRef Hoff SD, Bailey HR, Butts DR et al (1994) Ambulatory surgical hemorrhoidectomy—a solution to postoperative urinary retention? Dis Colon Rectum 37:1242–1244PubMedCrossRef
Metadata
Title
Randomized placebo-controlled trial on local applications of opioids after hemorrhoidectomy
Authors
G. Tegon
L. Pulzato
L. Passarella
D. Guidolin
M. Zusso
P. Giusti
Publication date
01-09-2009
Publisher
Springer Milan
Published in
Techniques in Coloproctology / Issue 3/2009
Print ISSN: 1123-6337
Electronic ISSN: 1128-045X
DOI
https://doi.org/10.1007/s10151-009-0518-y

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