fluvoxamine and Neuralgia

Paclitaxel is widely used in cancer chemotherapy for the treatment of solid tumors, but it frequently causes peripheral neuropathy. Milnacipran, a serotonin/noradrenaline reuptake inhibitor and fluvoxamine, a selective serotonin reuptake inhibitor, have shown efficacy against several chronic pain syndromes. In this study, we investigated the attenuation of paclitaxel-induced mechanical allodynia in mice by milnacipran and fluvoxamine. Paclitaxel was administered once per day (2 mg/kg, intraperitoneally (i.p.)) for 5 days to mice. Mechanical allodynia was evaluated by measuring the withdrawal response to stimulation with a von Frey filament. In paclitaxel-treated mice, mechanical allodynia was observed on days 3-15 of paclitaxel administration. A single administration of milnacipran (20 mg/kg, i.p.) or fluvoxamine (40 mg/kg, i.p.) had no effect on paclitaxel- induced mechanical allodynia. However, repeated administration of milnacipran (10, 20 mg/kg, once per day, i.p.) for 5 days significantly reduced paclitaxel-induced mechanical allodynia. In contrast, repeated fluvoxamine administration (40 mg/kg, once per day, i.p.) for 5 days resulted in a weak attenuation of paclitaxel-induced mechanical allodynia. These results suggest that chronic paclitaxel administration induces mechanical allodynia, and that repeated milnacipran administration may be an effective therapeutic approach for the treatment of neuropathic pain caused by paclitaxel treatment for cancer.

Topics: Animals; Cyclopropanes; Disease Models, Animal; Fluvoxamine; Hyperalgesia; Male; Mice; Milnacipran; Neuralgia; Paclitaxel

Diabetic neuropathic pain management is difficult even with non-steroidal anti-inflammatory drugs and narcotic analgesics such as morphine. Fluvoxamine, a class of selective serotonin reuptake inhibitors (SSRIs), is widely used to treat depression. Its analgesic effects are also documented for diabetic neuropathic pain, but they are limited because it is administered as a single-dose. In this study, we examined the time course of the antiallodynic effect of fluvoxamine in a rat model of diabetic neuropathic pain, which was induced by a single intraperitoneal administration of streptozotocin (75 mg/kg). In addition, the involvement of spinal serotonin (5-HT) receptors in long-term fluvoxamine treatment was studied by intrathecal administration of 5-HT receptor antagonists. In this study the development of mechanical hyperalgesia was assessed by measuring the hind paw withdrawal threshold using von Frey filaments. The results demonstrated that daily oral administration of fluvoxamine (10, 30, and 100 mg/kg) to diabetic rats from 3 to 8 weeks after streptozotocin administration resulted in a dose-dependent antiallodynic effect. The antiallodynic effect was sustained from 2 to 5 weeks after fluvoxamine administration. The antiallodynic effect of fluvoxamine in the diabetic rats was attenuated by WAY-100635 (a 5-HT(1A) receptor antagonist) intrathecally administered 1 week after the onset of daily administration of fluvoxamine, whereas no significant attenuation was seen when the antagonist was administered 3 and 5 weeks after fluvoxamine administration. The antiallodynic effect of fluvoxamine was also attenuated by ketanserin (a 5-HT(2A/2C) receptor antagonist) and ondansetron (a 5-HT3 receptor antagonist) intrathecally administered 1 and 3 weeks after the onset of daily fluvoxamine administration. However, no significant attenuation was observed when the antagonist was administered 5 weeks after fluvoxamine administration. This study demonstrated that daily oral administration of fluvoxamine can afford a sustained antiallodynic effect against streptozotocin-induced neuropathic pain. Furthermore, there appears to be a time-dependent relevance of different types of 5-HT receptors (5-HT(1A), 5-HT(2A/2C), and 5-HT3) to streptozotocin-induced diabetic neuropathic pain when treated with daily fluvoxamine.

Topics: Animals; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Fluvoxamine; Male; Neuralgia; Rats; Rats, Sprague-Dawley; Receptors, Serotonin; Selective Serotonin Reuptake Inhibitors; Streptozocin

There is an association between depression and chronic pain, and some antidepressants exert antinociceptive effects in humans and laboratory animals. We examined the effects of fluvoxamine, a selective serotonin reuptake inhibitor, on mechanical allodynia and its mechanism of action in the mouse chronic pain model, which was prepared by partially ligating the sciatic nerve. The antiallodynic effect was measured using the von Frey test. Fluvoxamine produced antiallodynic effects following both systemic and intrathecal administration. In 5-hydroxytryptamine (5-HT)-depleted mice, prepared by intracerebroventricular injection of 5,7-dihyroxytryptamine, the fluvoxamine-induced antiallodynic effect was significantly attenuated. The antiallodynic effects of systemic fluvoxamine were also reduced by both systemic and intrathecal administration of ketanserin, a 5-HT2A/2C receptor antagonist. In addition, fluvoxamine also induced antinociceptive effect in the acute paw pressure test, and this effect was antagonized by the 5-HT3 receptor antagonist granisetron. These results indicate that fluvoxamine exerts its antiallodynic effects on neuropathic pain via descending 5-HT fibers and spinal 5-HT2A or 5-HT2C receptors, and the antinociception on acute mechanical pain via 5-HT3 receptors.

Topics: Analysis of Variance; Animals; Area Under Curve; Disease Models, Animal; Dose-Response Relationship, Drug; Epinephrine; Fluvoxamine; Hyperalgesia; Male; Mice; Mice, Inbred Strains; Neuralgia; Pain Threshold; Receptor, Serotonin, 5-HT2A; Receptor, Serotonin, 5-HT2C; Selective Serotonin Reuptake Inhibitors; Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists; Time Factors

The involvement of opioid receptor activation in the antinociceptive effect of either fluvoxamine, a selective serotonin reuptake inhibitor, or serotonin (5-HT) on thermal hyperalgesia and mechanical allodynia in a model of neuropathic pain in mice induced by sciatic nerve ligation was examined. The experiments were conducted 2 or 6 weeks after unilateral sciatic nerve ligation. Ipsilateral thermal hyperalgesia and mechanical allodynia were observed both 2 and 6 weeks after sciatic nerve ligation. Neither s.c. fluvoxamine nor i.t. 5-HT affected sciatic nerve ligation-induced thermal hyperalgesia or mechanical allodynia in mice 2 weeks after sciatic nerve ligation. However, the same dose of either fluvoxamine or 5-HT significantly reduced mechanical allodynia but not thermal hyperalgesia in sciatic nerve ligated mice 6 weeks after surgery. The antinociceptive effect of fluvoxamine on sciatic nerve ligation-induced mechanical allodynia in mice 6 weeks after surgery was completely abolished by pretreatment with either naloxone, a nonselective opioid receptor antagonist, or beta-funaltrexamine, a selective mu-opioid receptor antagonist. Furthermore, pretreatment with naltrindole, a selective delta-opioid receptor antagonist, partially but significantly inhibited the antinociceptive effect of fluvoxamine in sciatic nerve ligated mice at the 6th postoperative week. The antinociceptive effect induced by i.t. 5-HT was also completely antagonized by either naloxone or beta-funaltrexamine, and partially inhibited by naltrindole. However, pretreatment with nor-binaltorphimine, a selective kappa-opioid receptor antagonist, had no effect against either s.c. fluvoxamine- or i.t. 5-HT-induced antinociception. These results suggest that the antinociceptive effect of s.c. fluvoxamine or i.t. 5-HT in the chronic state of sciatic nerve ligation-induced neuropathic pain may be related to opioidergic activity, mainly through the activation of spinal mu- and delta-opioid receptors.

Topics: Analgesics; Animals; Dose-Response Relationship, Drug; Fluvoxamine; Hyperalgesia; Injections, Spinal; Ketanserin; Male; Mice; Mice, Inbred ICR; Naloxone; Narcotic Antagonists; Neuralgia; Ondansetron; Receptors, Opioid; Sciatic Nerve; Selective Serotonin Reuptake Inhibitors; Serotonin; Serotonin Agents; Serotonin Antagonists; Time Factors

Case 1: female, age 76. Fluvoxamine (50 mg/day) initiated a reduction of pain on the 14th day of administration and completely ameliorated pain as well as depression. Case 2: female, age 76. Fluvoxamine (25 mg/day) was administered with tandospirone (15 mg/day) which augments the effect of an SSRI. This combination regimen induced a reduction of PHN-pain on the 10th day and as the analgesic effect attained nearly 50%, there occurred a reflaming of pain on the 35th day. Increasing fluvoxamine to 50 mg/day reameliorated pain on the 49th day, and a further increase to 75 mg/day finally eliminated pain and depression at the end of the 3rd month. The long latency of fluvoxamine action, its shortening by tandospirone and the parallel changes of PHN and depression are all indicative of that the same mechanism, namely renormalization of the dysfunctioned central serotonergic transmission would be underlying both the anti-PHN and antidepressant actions. It would be concluded that fluvoxamine alleviates PHN by restoration of the descending serotonergic inhibition of primary afferent activity that carries pain impulses.

Topics: Aged; Chronic Disease; Drug Therapy, Combination; Female; Fluvoxamine; Herpes Zoster; Humans; Isoindoles; Neuralgia; Piperazines; Pyrimidines; Selective Serotonin Reuptake Inhibitors; Serotonin Receptor Agonists; Treatment Outcome