Spinal 5-HT(2) and 5-HT(3) Receptors Mediate Low, but Not High, Frequency TENS-induced Antihyperalgesia in Rats

Overview

Journal Pain

Specialties Neurology
Psychiatry

Date 2003 Sep 23

PMID 14499437

Citations 46

Authors

Rajan Radhakrishnan

Ellen W King

Janelle K Dickman

Carli A Herold

Natalie F Johnston

Megan L Spurgin

Kathleen A Sluka

Affiliations

Soon will be listed here.

Abstract

Transcutaneous electrical nerve stimulation (TENS) is a form of non-pharmacological treatment for pain. Involvement of descending inhibitory systems is implicated in TENS-induced analgesia. In the present study, the roles of spinal 5-HT and alpha(2)-adrenoceptors in TENS analgesia were investigated in rats. Hyperalgesia was induced by inflaming the knee joint with 3% kaolin-carrageenan mixture and assessed by measuring paw withdrawal latency (PWL) to heat before and 4 h after injection. The (1). alpha(2)-adrenergic antagonist yohimbine (30 microg), (2). 5-HT antagonist methysergide (5-HT(1). and 5-HT(2). 30 microg), one of the 5-HT receptor subtype antagonists, (3). NAN-190 (5-HT(1A), 15 microg), (4). ketanserin (5-HT(2A), 30 microg), (5). MDL-72222 (5-HT(3), 12 microg), or (6). vehicle was administered intrathecally prior to TENS treatment. Low (4 Hz) or high (100 Hz) frequency TENS at sensory intensity was then applied to the inflamed knee for 20 min and PWL was determined. Selectivity of the antagonists used was confirmed using respective agonists administered intrathecally. Yohimbine had no effect on the antihyperalgesia produced by low or high frequency TENS. Methysergide and MDL-72222 prevented the antihyperalgesia produced by low, but not high, frequency TENS. Ketanserin attenuated the antihyperalgesic effects of low frequency TENS whereas NAN-190 had no effect. The results from the present study show that spinal 5-HT receptors mediate low, but not high, frequency TENS-induced antihyperalgesia through activation of 5-HT(2A) and 5-HT(3) receptors in rats. Furthermore, spinal noradrenergic receptors are not involved in either low or high frequency TENS antihyperalgesia.

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References

Sluka K, Deacon M, Stibal A, Strissel S, Terpstra A . Spinal blockade of opioid receptors prevents the analgesia produced by TENS in arthritic rats. J Pharmacol Exp Ther. 1999; 289(2):840-6. View

Janko M, Trontelj J . Transcutaneous electrical nerve stimulation: a microneurographic and perceptual study. Pain. 1980; 9(2):219-230. DOI: 10.1016/0304-3959(80)90009-3. View

Giordano J . Analgesic profile of centrally administered 2-methylserotonin against acute pain in rats. Eur J Pharmacol. 1991; 199(2):233-6. DOI: 10.1016/0014-2999(91)90462-y. View

Chandran P, Sluka K . Development of opioid tolerance with repeated transcutaneous electrical nerve stimulation administration. Pain. 2003; 102(1-2):195-201. DOI: 10.1016/s0304-3959(02)00381-0. View

Zeitz K, Guy N, Malmberg A, Dirajlal S, Martin W, Sun L . The 5-HT3 subtype of serotonin receptor contributes to nociceptive processing via a novel subset of myelinated and unmyelinated nociceptors. J Neurosci. 2002; 22(3):1010-9. PMC: 6758503. View

Milne S, Welch V, Brosseau L, Saginur M, Shea B, Tugwell P . Transcutaneous electrical nerve stimulation (TENS) for chronic low back pain. Cochrane Database Syst Rev. 2001; (2):CD003008. DOI: 10.1002/14651858.CD003008. View

. Effects of electrolytic lesions or intracerebral injections of 5,6-dihydroxytryptamine in raphe nuclei on acupuncture analgesia in rats. Chin Med J (Engl). 1979; 92(2):129-36. View

Aimone L, Jones S, Gebhart G . Stimulation-produced descending inhibition from the periaqueductal gray and nucleus raphe magnus in the rat: mediation by spinal monoamines but not opioids. Pain. 1987; 31(1):123-136. DOI: 10.1016/0304-3959(87)90012-1. View

Goodchild C, Guo Z, Freeman J, Gent J . 5-HT spinal antinociception involves mu opioid receptors: cross tolerance and antagonist studies. Br J Anaesth. 1997; 78(5):563-9. DOI: 10.1093/bja/78.5.563. View

10.

Bardin L, Lavarenne J, Eschalier A . Serotonin receptor subtypes involved in the spinal antinociceptive effect of 5-HT in rats. Pain. 2000; 86(1-2):11-8. DOI: 10.1016/s0304-3959(99)00307-3. View

11.

Danzebrink R, Gebhart G . Intrathecal coadministration of clonidine with serotonin receptor agonists produces supra-additive visceral antinociception in the rat. Brain Res. 1991; 555(1):35-42. DOI: 10.1016/0006-8993(91)90856-q. View

12.

Hoyer D, Clarke D, Fozard J, Hartig P, Martin G, Mylecharane E . International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin). Pharmacol Rev. 1994; 46(2):157-203. View

13.

Liss S, Liss B . Physiological and therapeutic effects of high frequency electrical pulses. Integr Physiol Behav Sci. 1996; 31(2):88-95. DOI: 10.1007/BF02699781. View

14.

Jensen T, Yaksh T . Comparison of the antinociceptive effect of morphine and glutamate at coincidental sites in the periaqueductal gray and medial medulla in rats. Brain Res. 1989; 476(1):1-9. DOI: 10.1016/0006-8993(89)91529-1. View

15.

Eide P, Hole K . The role of 5-hydroxytryptamine (5-HT) receptor subtypes and plasticity in the 5-HT systems in the regulation of nociceptive sensitivity. Cephalalgia. 1993; 13(2):75-85. DOI: 10.1046/j.1468-2982.1993.1302075.x. View

16.

Oyama T, Ueda M, Kuraishi Y, Akaike A, Satoh M . Dual effect of serotonin on formalin-induced nociception in the rat spinal cord. Neurosci Res. 1996; 25(2):129-35. DOI: 10.1016/0168-0102(96)01034-6. View

17.

Osiri M, Welch V, Brosseau L, Shea B, McGowan J, Tugwell P . Transcutaneous electrical nerve stimulation for knee osteoarthritis. Cochrane Database Syst Rev. 2000; (4):CD002823. DOI: 10.1002/14651858.CD002823. View

18.

Hamon M, Gallissot M, Menard F, Gozlan H, Bourgoin S, Verge D . 5-HT3 receptor binding sites are on capsaicin-sensitive fibres in the rat spinal cord. Eur J Pharmacol. 1989; 164(2):315-22. DOI: 10.1016/0014-2999(89)90472-x. View

19.

Miller J, Proudfit H . Antagonism of stimulation-produced antinociception from ventrolateral pontine sites by intrathecal administration of alpha-adrenergic antagonists and naloxone. Brain Res. 1990; 530(1):20-34. DOI: 10.1016/0006-8993(90)90653-s. View

20.

Melzack R, WALL P . Pain mechanisms: a new theory. Science. 1965; 150(3699):971-9. DOI: 10.1126/science.150.3699.971. View