Korean J Pain.  2013 Apr;26(2):125-129. 10.3344/kjp.2013.26.2.125.

Effects of Palonosetron, a 5-HT3 Receptor Antagonist, on Mechanical Allodynia in a Rat Model of Postoperative Pain

• Jung KT
• Yoon MH
• Lee HY
• Yu BY
• Kim DK
• Lim KJ

• KMID: 1978655
• DOI: http://doi.org/10.3344/kjp.2013.26.2.125

Abstract

BACKGROUND
5-hydroxytryptamine 3 (5-HT3) receptors have been known to be associated with the modulation of nociceptive transmission. However, it is uncertain whether 5-HT3 plays a role in the antinociceptive or pronociceptive pathway for incisional pain. In this study, we evaluated the effects of palonosetron, a 5-HT3 receptor antagonist, on incisional pain in rats when administered intrathecally or intraplantarly.
METHODS
An intrathecal catheter was implanted through the cisterna magna and placed in the intrathecal space of rats. An incision in the plantaris muscle of the right hind paw was done under anesthesia with sevoflurane. Withdrawal thresholds were evaluated with the von Frey filament after 2 hours. Palonosetron (0.5 and 0.1 microg intrathecally; 0.5 microg intraplantarly) was administered and the thresholds were observed for 4 hours.
RESULTS
Mechanical hypersensitivity developed after the incision. Intrathecal palonosetron (0.5 microg and 0.1 microg) did not alter the paw withdrawal threshold. Intraplantar palonosetron (0.5 microg) also did not change the paw withdrawal threshold.
CONCLUSIONS
Intrathecal and intraplantar palonosetron (0.5 microg) had no effect on modulating the mechanical hypersensitivity in the incisional pain model of rats.

Keyword

5-HT3 receptor; nociceptive pain; pain threshold; palonosetron; Sprague-Dawley rats

MeSH Terms

Anesthesia
Animals
Catheters
Cisterna Magna
Hyperalgesia
Hypersensitivity
Isoquinolines
Methyl Ethers
Muscle, Skeletal
Nociceptive Pain
Pain Threshold
Pain, Postoperative
Quinuclidines
Rats
Rats, Sprague-Dawley
Receptors, Serotonin, 5-HT3
Serotonin
Isoquinolines
Methyl Ethers
Quinuclidines
Receptors, Serotonin, 5-HT3
Serotonin

Figure

• 

  Fig. 1 Withdrawal threshold in rats treated with intrathecal injection of palonosetron. Both of 0.5 µg and 0.1 µg of palonosetron did not increase the withdrawal threshold after incision significantly. Baseline is before the incision of the plantaris muscle. Control is 2 hours after incision.

• 

  Fig. 2 Withdrawal threshold in rats treated with intraplantar injection of palonosetron 0.5 µg. Intraplantar injection of palonosetron did not increase the withdrawal threshold after incision significantly. Baseline is before the incision of the plantaris muscle. Control is 2 hours after incision.

Reference

1. Faerber L, Drechsler S, Ladenburger S, Gschaidmeier H, Fischer W. The neuronal 5-HT3 receptor network after 20 years of research--evolving concepts in management of pain and inflammation. Eur J Pharmacol. 2007; 560:1–8. PMID: 17316606.

2. Jeong CY, Bae HB, Park HC, Choi JI, Yoon MH. Evaluation of the role of 5-hydroxytryptamine receptor subtypes in the regulation of nociceptive transmission in the rat spinal cord. Korean J Anesthesiol. 2004; 47:856–861.

3. Ali Z, Wu G, Kozlov A, Barasi S. The role of 5HT3 in nociceptive processing in the rat spinal cord: results from behavioural and electrophysiological studies. Neurosci Lett. 1996; 208:203–207. PMID: 8733305.

4. McCleane GJ, Suzuki R, Dickenson AH. Does a single intravenous injection of the 5HT3 receptor antagonist ondansetron have an analgesic effect in neuropathic pain? A double-blinded, placebo-controlled cross-over study. Anesth Analg. 2003; 97:1474–1478. PMID: 14570668.

5. Yaksh TL, Rudy TA. Chronic catheterization of the spinal subarachnoid space. Physiol Behav. 1976; 17:1031–1036. PMID: 14677603.

6. Brennan TJ, Vandermeulen EP, Gebhart GF. Characterization of a rat model of incisional pain. Pain. 1996; 64:493–501. PMID: 8783314.

7. Shin DJ, Yoon MH, Lee HG, Kim WM, Park BY, Kim YO, et al. The effect of treatment with intrathecal ginsenosides in a rat model of postoperative pain. Korean J Pain. 2007; 20:100–105.

8. Wong EH, Clark R, Leung E, Loury D, Bonhaus DW, Jakeman L, et al. The interaction of RS 25259-197, a potent and selective antagonist, with 5-HT3 receptors, in vitro. Br J Pharmacol. 1995; 114:851–859. PMID: 7773546.

9. Kovac AL, Eberhart L, Kotarski J, Clerici G, Apfel C. Palonosetron 04-07 Study Group. A randomized, doubleblind study to evaluate the efficacy and safety of three different doses of palonosetron versus placebo in preventing postoperative nausea and vomiting over a 72-hour period. Anesth Analg. 2008; 107:439–444. PMID: 18633021.

10. Alhaider AA, Lei SZ, Wilcox GL. Spinal 5-HT3 receptor-mediated antinociception: possible release of GABA. J Neurosci. 1991; 11:1881–1888. PMID: 2066767.

11. Suzuki R, Rygh LJ, Dickenson AH. Bad news from the brain: descending 5-HT pathways that control spinal pain processing. Trends Pharmacol Sci. 2004; 25:613–617. PMID: 15530638.

12. Suzuki R, Morcuende S, Webber M, Hunt SP, Dickenson AH. Superficial NK1-expressing neurons control spinal excitability through activation of descending pathways. Nat Neurosci. 2002; 5:1319–1326. PMID: 12402039.

13. Rahman W, Suzuki R, Hunt SP, Dickenson AH. Selective ablation of dorsal horn NK1 expressing cells reveals a modulation of spinal alpha2-adrenergic inhibition of dorsal horn neurones. Neuropharmacology. 2008; 54:1208–1214. PMID: 18462764.

14. Oatway MA, Chen Y, Weaver LC. The 5-HT3 receptor facilitates at-level mechanical allodynia following spinal cord injury. Pain. 2004; 110:259–268. PMID: 15275776.

15. Vandermeulen EP, Brennan TJ. Alterations in ascending dorsal horn neurons by a surgical incision in the rat foot. Anesthesiology. 2000; 93:1294–1302. PMID: 11046219.

16. Zahn PK, Pogatzki EM, Brennan TJ. Mechanisms for pain caused by incisions. Reg Anesth Pain Med. 2002; 27:514–516. PMID: 12373702.

17. Pogatzki EM, Urban MO, Brennan TJ, Gebhart GF. Role of the rostral medial medulla in the development of primary and secondary hyperalgesia after incision in the rat. Anesthesiology. 2002; 96:1153–1160. PMID: 11981156.

18. Zeitz KP, Guy N, Malmberg AB, Dirajlal S, Martin WJ, Sun L, et al. The 5-HT3 subtype of serotonin receptor contributes to nociceptive processing via a novel subset of myelinated and unmyelinated nociceptors. J Neurosci. 2002; 22:1010–1019. PMID: 11826129.

19. Rahman W, Suzuki R, Webber M, Hunt SP, Dickenson AH. Depletion of endogenous spinal 5-HT attenuates the behavioural hypersensitivity to mechanical and cooling stimuli induced by spinal nerve ligation. Pain. 2006; 123:264–274. PMID: 16644129.

20. Kress M, Reeh PW, Vyklicky L. An interaction of inflammatory mediators and protons in small diameter dorsal root ganglion neurons of the rat. Neurosci Lett. 1997; 224:37–40. PMID: 9132685.

21. Sommer C. Is serotonin hyperalgesic or analgesic? Curr Pain Headache Rep. 2006; 10:101–106. PMID: 16539862.

22. Eschalier A, Kayser V, Guilbaud G. Influence of a specific 5-HT3 antagonist on carrageenan-induced hyperalgesia in rats. Pain. 1989; 36:249–255. PMID: 2919105.

23. Park SK, Cho EJ. A randomized, double-blind trial of palonosetron compared with ondansetron in preventing postoperative nausea and vomiting after gynaecological laparoscopic surgery. J Int Med Res. 2011; 39:399–407. PMID: 21672343.