Abstract
The clinical usefulness of classical tricyclic antidepressants has been indicated in a variety of neuropathic pain. The role of selective serotonin reuptake inhibitors (SSRIs) is, however, controversial in pain control. The present study was aimed at evaluating the efficacy of an SSRI, fluoxetine, in neuropathic pain involving peripheral (carrageenan-induced inflammation) and central sensitization (spinal nerve ligation) in rats. Fluoxetine was also assessed for antinociceptive and antiphlogistic effect against acetic acid-induced chemonociception in mice and carrageenan-induced inflammation. Fluoxetine (100-400 μg, intraplantar administration) failed to attenuate either hyperalgesia or cold allodynia in any of the tests employed. Fluoxetine dose dependently increased paw volume in the absence or presence of an inflammatory stimulus which was not reversed by indomethacin (10 mg/kg, p.o). Fluoxetine was ineffective in reducing hyperalgesia and allodynia associated with the rat models. However, fluoxetine dose dependently decreased acetic acid-induced writhings. The results indicated that 5-HT plays a differential role in pain modulation and may not be playing a major role in the maintenance of hyperalgesia and allodynia in the rat models.
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REFERENCES
Abbott, F. V. (1992). Contributions of tricyclic antidepressants in a new model of mononeuropathy in rats, Pain 49 279–289.
Allen, M. and Taylor R. (1999). Pain control in palliative care, Pharm. J. 262, 620–624.
Bianchi, M., Rossini, G., Sacerdote, P., et al. (1995). Effects of clomipramine-induced inflammation in rats, Inflamm. Res. 44, 466–469.
Coderre, T. J., Vaccarino, A. L. and Melzack, R. (1990). Central nervous system plasticity in the tonic pain response to subcutaneous formalin injection, Brain Res. 535, 155–158.
Doak, G. J. and Sawynok, J. S. (1991). Formalin-induced nociceptive behavior and edema: Involvement of 5-hydoxytryptaminereceptor subtypes. Neuroscience 45, 761–765.
Dubner, R. and Ruda, M. A. (1996). Activity dependent neural plasticity following tissue injury and inflammation, TIPS 15, 96–103.
Eisenach, J. and Gebhart, G. F. (1995). Intrathecal amitryptyline acts as an N-methyl-D-aspartate receptor antagonist in the presence of inflammatory hyperal gesia in rats, Pain 83, 1046–1054.
Filho, R. R. and Takashi, R. N. (1999). Antinociceptive effects induced by desipramine and fluoxetine are dissociated from their antidepressant or anxiolytic action in mice, Int J. Neuropsychopharmacology 2, 263–269.
Gonzalez, M. I., Field., Hughes. J., et al. (2000). Evaluation of selective NK1 receptor antagonist C1-1021 in animal models of inflammatory and neuropathic pain, J. Pharm. Exp. Ther. 294, 444–450.
Hawang, A. S. and Wilcox, G. L. (1987). Analgesic properties of intrathecally administered heterocyclic antidepressants. Pain 28, 343–355.
Iwashita, T. and Shimizu T. (1992). Imipramine inhibits intrathecal substance P receptor in mice. Brain Res. 581, 59–66.
Jain, N. K. and Kulkarni, S. K. (1999). Antinociceptive effects of Tanacetum parthenium L. extract in mice and rats, J. Ethnopharmacol. 68, 251–259.
Jain, N. K. and Kulkarni, S. K. (2001). Pharmacological and pharmacokinetic studies on marketed gel preprations of nimusilide. Ind. Drugs 38(2), 63–66.
Jain, N. K., Singh. A. and Kulkarni, S. K. (1999). Analgesic, anti-inflammatory and ulcerogenic activity of a zinc-naproxen complex in mice and rats. Pharm. Pharmacol. Commun. 5, 599–602.
Jett, M. F., McGuirk, J., Waligora, D., et al. (1997). The effects of mexilitine, desipramine and fluoxetine in rat models involving central sensitization. Pain 69, 161–169.
McQuay, H. and Tramer, M. (1995). A systematic review of antidepressants in neuropathic pain. Brit. Med. J. 311, 1047–1052.
Sawynok, J., Jessar, M. and Reid, A. R. (1999). Peripheral nociceptive actions of desipramine and fluoxetine in an inflammatory and neuropathic pain test in the rat. Pain 82, 149– 158.
Sinnott, C. (1998). Neuropathic pain. CME Bulletin: palliative medicine 1, 7–9.
Su, X. and Gebhart, G. F. (1998). Effects of tricyclic antidepressantson mechanosensitivepelvic nerve afferent fibers in the rat colon. Pain 76, 105–114.
Sufka, K. J., Sehomburg, F. M. and Giordano, J. (1991). Receptor mediation of 5-HT in-flammation and nociception in rats. Pharmacol. Biochem. Behav. 41, 53–56.
Wall, P. D. (1997). Neuropathic pain. Pain 70, 109–115.
Wang, Y. X., Bowersox, S. S., Pettus, M., et al. (1999). Antinociceptive properties of fenfluramine. A serotonin reuptake inhibitor, in a rat model of neuropathy. J. Pharm. Exp. Ther. 291, 1008– 1016.
Watson, C. P. N., Chipman, M., Reed, K., et al. (1992). Amitryptyline versus maprotiline in post-therapeutic neuralgia: a randomized, double blind, crossover trial. Pain 48, 29–36.
Woolf, C. J. (1983). Evidence for a critical component of post-injury pain hypersensitivity. Nature 306, 686–688.
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Pal Singh, V., Jain, N.K. & Kulkarni, S.K. Fluoxetine, a selective serotonin reuptake inhibitor modulates inflammatory and neuropathic pain in the rat. Inflammopharmacology 9, 219–228 (2001). https://doi.org/10.1163/156856001760209761
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DOI: https://doi.org/10.1163/156856001760209761