The Roles of the Opioidergic System and Nitric Oxide in the Analgesic Effect of Venlafaxine

Abstract

The noradrenalin and serotonin re-uptake inhibitor venlafaxine has an analgesic eŠect that is independent of its antidepressant activity; however, the mechanism of this eŠect remains to be elucidated. This study was performed to investigate the possible roles of the opioidergic system and nitric oxide (NO) pathway in the analgesic eŠect of venlafaxine. Eighty Wistar rats of both sexes were allocated to 10 groups. The hot plate test was used to assess the antinociceptive/ analgesic eŠect. The temperature of the hot plate was adjusted to 52.5±1°C, the cut oŠ period was set to be 50 sec; licking of the hind paw was used as a sign of pain perception. Venlafaxine alone (25 mg/kg) showed marked analgesic activity (p＜0.05). N-v-nitro L-arginine (L-NOARG) alone (20 mg/kg) and naloxone alone (2 mg/kg and 4 mg/kg) showed no analgesic activity (p＞0.05). Coadministration of low-dose naloxone (2 mg/kg) and both doses of L-NOARG (20 and 40 mg/kg) with venlafaxine (25 mg/kg) did not modify the analgesic eŠect but high-dose naloxone (4 mg/kg) decreased it signiˆcantly (p＜0.05). In conclusion, these results suggest that the opioidergic system but not the NO pathway has a role in the analgesic eŠect of venlafaxine.

Monoaminergic Antidepressants in the Relief of Pain: Potential Therapeutic Utility of Triple Reuptake Inhibitors (TRIs)

“…At the supraspinal level, milnacipran attenuates the increase in c-fos expression in the ACC in response to noxious stimulation [299]. Surprisingly, in contrast to duloxetine and milnacipran, venlafaxine produced antinociceptive effects in mice and rats in acute pain assessed in the hotplate test [303,304,311]. Although venlafaxine has a weak affinity for 5-HT and NE transporters in comparison with duloxetine and milnacipran, the reasons of such difference remain obscure.…”

A study of antinociceptive effect of venlafaxine in albino mice

“…When high dose of naloxone (4mg/kg) was administered along with Venlafaxine (22mg/kg), analgesic activity decreased significantly. 16 This study shows that antinociceptive activity of Venlafaxine may be because of its action on opioid receptors like morphine or Pethidine.…”

Ellagic acid enhances the antinociceptive action of venlafaxine in mouse acetic acid-induced pain: An isobolographic analysis

“…VLF has also shown to relieve pain in patients with diabetic neuropathy, painful polyneuropathy and fibromyalgia [13,[32][33][34]. It has been reported that the somatodendritic 5-HT1A [16], k-or d-opioid [14], and a 2 -adrenergic [15] receptor systems are involved in the antinociception produced by VLF. Also, It has been reported that VLF produced dose-dependent antinociceptive activity in writhing test, which is consistent with our results [10,11].…”

“…VLF mainly has a central site of action through interaction with monoamine transporter and also opioid and non-opioid receptor systems [14][15][16]. Therefore, the synergistic antinociceptive interaction between EA and VLF may occur at peripheral and/ or the central level.…”

“…It increases the inhibiting tone of serotonergic and norepinephrine descending pathways in the brain [11]. Also, it has been shown that VLF antinociception could be mediated through the k-and d-opioid [14], a 2 -adrenergic [15] and 5-HT1A receptor [16] systems.…”