Behavioral and electrophysiological abnormalities in two rat models of antiretroviral drug-induced neuropathy

Abstract

Painful peripheral neuropathy due to the antiretroviral therapy used to treat HIV is one of the most prevalent side effects occurring in at least 30% of patients living with this infection. We have evaluated the electrophysiological and behavioral effects of d4T and ddC on peripheral large and small nerve fibers in male rats treated with d4T (Sprague-Dawley, 50 mg/kg, twice within 1 week), ddC (Wistar, 50 mg/kg, 3 times per week for 3 weeks), or vehicle. The effect of the interventions was assessed using behavioral measures of mechanical sensitivity, conventional nerve conduction studies, and microneurographic single nerve C-fiber recordings. To mimic as much as possible the human clinical condition, all treated animals were included in the study. No statistically significant differences were observed in behavioral parameters of mechanical sensitivity. Nerve conduction studies did not reveal any significant change in the ddC-treated group. In contrast, we observed electrophysiological evidence of significant demyelinating neuropathy 1 week after the start of d4T treatment. Additionally, spontaneous activity in mechanoinsensitive C-nociceptors was observed in both drug-treated groups. No relationship could be established between measures of spontaneous activity in C-nociceptors and the results of the behavioral tests. Our results show that both models of antiretroviral-induced neuropathy differ in their effects on peripheral nerves. However, both groups present abnormal spontaneous activity in mechanoinsensitive C-nociceptors that can be used as a model for pharmacological intervention.

Behavioural, morphological and electrophysiological assessment of the effects of type 2 diabetes mellitus on large and small nerve fibres in Zucker diabetic fatty, Zucker lean and Wistar rats

“…Amplitude and NCV of sensory nerve action potential (SNAP) and compound muscle action potential (CMAP) were recorded as previously described (Garcia‐Perez et al., ). Briefly, NCV was recorded from the tail using conventional clinical‐grade equipment (Medelec Synergy N2 EMG System, Viasys Healthcare, Madison, USA) employing recording and stimulating stainless steel needle electrodes.…”

“…We have previously demonstrated that microneurography has been successfully employed to reveal neural characteristics of C‐nociceptors’ activity in patients and animal models of neuropathic pain (Serra et al., , , ; Garcia‐Perez et al., ). Moreover, recording of spontaneous discharges in different types of C‐fibres identified by a latency‐based marking method has become an important tool to identify abnormalities in neural traffic of C‐nociceptors.…”

Neurological Health in Sexual and Gender Minority Individuals

“…The authors suggested that this was due to spironolactone, the antiandrogen she had taken for 15 years, which also has proandrogenic activity. 86 Another case report described a transgender man with hypokalemic thyrotoxic periodic paralysis exacerbated by testosterone therapy, suggesting that the androgenic effect of testosterone on the Na þ/K þ -ATPase pumps contributed to hypokalemia and requiring this patient to stop taking GAHT. 87…”

Neuropathy complication of antiretroviral therapy in HIV/AIDS patients

“…This group includes medications zidovudine or azidothymidine, didanosine, zalcitabine (ddC), stavudine (d4T), lamivudine, and abacavir. ddC was one of the first HIV/AIDS‐approved antiretrovirals and is now considered to be the most neurotoxic (Garcia‐Perez, Solà, Sumalla, & Serra, 2015) The introduction of combination antiretroviral therapy (cART) dramatically reduced the morbidity and mortality associated with HIV among patients who have access to treatment. (Mwesiga, Kaddumukasa, Mugenyi, & Nakasujja, 2019).…”