Abstract
At least one third of HIV‐1‐afflicted individuals experience peripheral neuropathy. Although the underlying mechanisms are not known, they may involve neurotoxic HIV‐1 proteins. We assessed the influence of the neurotoxic HIV‐1 regulatory protein, Tat, on inflammatory and neuropathic nociceptive behaviors using transgenic male and female transgenic mice that conditionally expressed (or did not express) HIV‐1 Tat1‐86 in glial fibrillary acidic protein‐expressing glia in the central and peripheral nervous systems. Tat induction significantly attenuated the time spent paw‐licking following formalin injection (2.5%, i.pl.) in both male and female mice. However, significant sex differences were observed in the onset and magnitude of inflammation and sensory sensitivity following complete Freund’s adjuvant (CFA) injection (10%, i.pl.) after Tat activation. Unlike female mice, males showed a significant attenuation of paw swelling and an absence of mechanical/thermal hypersensitivity in response to CFA after Tat induction. Male Tat(+) mice also showed accelerated recovery from chronic constrictive nerve injury (CCI)‐induced neuropathic mechanical and thermal hypersensitivity compared to female Tat(+) mice. Morphine (3.2 mg/kg) fully reversed CCI‐induced mechanical hypersensitivity in female Tat(−) mice, but not in Tat(+) females. The ability of Tat to decrease edema, paw swelling, and limit allodynia suggest a sequela of events in which Tat‐induced functional deficits precede the onset of mechanical hypersensitivity. Moreover, HIV‐1 Tat attenuated responses to inflammatory and neuropathic insults in a sex‐dependent manner. HIV‐1 Tat appears to directly contribute to HIV sensory neuropathy and reveals sex differences in HIV responsiveness and/or the underlying peripheral neuroinflammatory and nociceptive mechanisms.
from Wiley: European Journal of Pain: Table of Contents https://ift.tt/3hoz0al
via IFTTT
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