Beneficial effects of octreotide in alcohol-induced neuropathic pain. Role of H(2)S, BDNF, TNF-α and Nrf2

PURPOSE: To explore the role and molecular mechanisms of neuroprotective effects of octreotide in alcohol-induced neuropathic pain. METHODS: Male Wistar rats were employed and were administered a chronic ethanol diet containing 5% v/v alcohol for 28 days. The development of neuropathic pain was assessed using von Frey hair (mechanical allodynia), pinprick (mechanical hyperalgesia) and cold acetone drop tests (cold allodynia). The antinociceptive effects of octreotide (20 and 40 µg·kg(–1)) were assessed by its administration for 28 days in ethanol-treated rats. ANA-12 (0.25 and 0.50 mg·kg(–1)), brain-derived neurotrophic factor (BDNF) receptor blocker, was coadministered with octreotide. The sciatic nerve was isolated to assess the biochemical changes including hydrogen sulfide (H(2)S), cystathionine β synthase (CBS), cystathionine γ lyase (CSE), tumor necrosis factor-α (TNF-α), BDNF and nuclear factor erythroid 2-related factor 2 (Nrf2). RESULTS: Octreotide significantly attenuated chronic ethanol-induced neuropathic pain and it also restored the levels of H(2)S, CBS, CSE, BDNF, Nrf2 and decreased TNF-α levels. ANA-12 abolished the effects of octreotide on pain, TNF-α, BDNF, Nrf2 without any significant effects on H(2)S, CBS, CSE. CONCLUSIONS: Octreotide may attenuate the behavioral manifestations of alcoholic neuropathic pain, which may be due to an increase in H(2)S, CBS, CSE, BDNF, Nrf2 and a decrease in neuroinflammation.