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Conditional expression of HIV‐1 tat in the mouse alters the onset and progression of tonic, inflammatory and neuropathic hypersensitivity in a sex‐dependent manner
Author(s) -
Bagdas Deniz,
Paris Jason J.,
Carper Moriah,
Wodarski Rachel,
Rice Andrew S. C.,
Knapp Pamela E.,
Hauser Kurt F.,
Damaj M. Imad
Publication year - 2020
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/ejp.1618
Subject(s) - licking , neuropathic pain , medicine , nociception , hyperalgesia , peripheral neuropathy , glial fibrillary acidic protein , immunology , inflammation , pharmacology , endocrinology , receptor , immunohistochemistry , diabetes mellitus
Background 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. Methods We 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 Tat 1‐86 in fibrillary acidic protein‐expressing glia in the central and peripheral nervous systems. Results 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, 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. Conclusions The 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.