• Deniz Bagdas, Jason J Paris, Moriah Carper, Rachel Wodarski, RiceAndrew S CASCPain Research Group, Department of Surgery and Cancer, Imperial College, London, UK., Pamela E Knapp, Kurt F Hauser, and M Imad Damaj.
• Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA, USA.
• Eur J Pain. 2020 Sep 1; 24 (8): 160916231609-1623.

BackgroundAt 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.MethodsWe assessed the influence of the neurotoxic HIV-1 regulatory protein, Tat, on inflammatory and neuropathic nociceptive behaviours using transgenic male and female mice that conditionally expressed (or did not express) HIV-1 Tat1-86 in fibrillary acidic protein-expressing glia in the central and peripheral nervous systems.ResultsTat 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, male mice 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.ConclusionsThe ability of Tat to decrease oedema, paw swelling, and limit allodynia suggests a sequel 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.© 2020 European Pain Federation - EFIC®.

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