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

ABSTRACT 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 (H2S), 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 H2S, 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 H2S, CBS, CSE. Conclusions Octreotide may attenuate the behavioral manifestations of alcoholic neuropathic pain, which may be due to an increase in H2S, CBS, CSE, BDNF, Nrf2 and a decrease in neuroinflammation.

Dor neuropática em pacientes com HIV/AIDS em uso de terapia antirretroviral / Neuropathic pain in HIV/AIDS patients using antiretroviral therapy

A infecção pelo vírus da imunodeficiência humana (HIV) representa um dos maiores problemas de saúde da atualidade em virtude de seu caráter pandêmico e gravidade. O uso da terapia antirretroviral está associado ao desenvolvimento de diferentes tipos de dor, sendo a dor neuropática uma delas. A dor neuropática ocorre pela lesão do sistema nociceptivo, que envolve mudanças moleculares, fisiológicas e anatômicas. Considerando que a infecção por HIV gera custos elevados para o sistema de saúde, e que suas comorbidades elevam ainda mais esses custos, a compreensão dos mecanismos da dor nessa população possibilita uma melhor assistência e uma redução da carga para o sistema. A dor neuropática pode apresentar diferentes possíveis mecanismos fisiopatológicos envolvidos, tornando-se um desafio para o tratamento de pacientes com HIV. A compreensão sobre a neurofisiologia da dor neuropática e o HIV pode promover melhores abordagens aos pacientes e a redução de comorbidades associadas, com impacto na qualidade de vida (AU)

Human immunodeficiency virus (HIV) infection is a major health problem nowadays due to its pandemic character and severity. The use of antiretroviral therapy is associated with the development of different types of pain, and neuropathic pain is one of them. Neuropathic pain is caused by an injury to the nociceptive system, which involves molecular, physiological and anatomical changes. Considering that HIV infection generates high costs for the health system, and that its comorbidities raise such costs even more, understanding the mechanisms of pain in this population can result in better care practices and reduction of burden to the system. Neuropathic pain may present different pathophysiological mechanisms becoming a challenge for HIV treatment. The understanding of the neurophysiology of neuropathic pain and the HIV can promote better patient approaches and the reduction of associated comorbidities with an impact on quality of life (AU)

Effect of Anorexia and Neuropathic Pain Induced by Cisplatin on Hindlimb Muscles of Rat

PURPOSE: The purpose of this study was to examine the effect of anorexia and neuropathic pain induced by cisplatin on hindlimb muscles of rats. METHODS: Adult male Sprague-Dawley rats were divided into two groups, a cisplatin-treated group (n=10) and a control group (n=10). In the cisplatin-treated group, cisplatin at a dose of 2 mg/kg was injected intraperitoneally two times a week up to a cumulative dose of 20 mg/kg over 5 weeks, and in the control group saline (0.9% NaCl) was injected intraperitoneally at the same dose and duration as the cisplatin-treated group. At 34 days all rats were anesthetized, after which the soleus and plantaris muscles were dissected. Withdrawal threshold, body weight, food intake, activity, muscle weight, Type I and II fiber cross-sectional areas and myofibrillar protein content of the dissected muscles were determined. RESULTS: Compared with the control group, the cisplatin-treated group showed significant decreases (p<.05) in withdrawal threshold, activity, food intake, body weight, Type I and II fiber cross-sectional areas, myofibrillar protein content and weight of the soleus and plantaris muscles. CONCLUSION: Muscular atrophy in hindlimb occurs due to anorexia and neuropathic pain induced by the cisplatin treatment.