Brain levels of the neurotransmitter γ-aminobutyric acid are reduced in people with HIV-related neuropathic pain.

Previous studies suggest a dysregulation of the inhibitory γ -aminobutyric acid (GABA) and the excitatory glutamate/glutamine (Glx) neurotransmitter systems in people living with chronic pain. Here, we test this hypothesis in people with HIV (PWH) on stable antiretroviral therapy, either with or without neuropathic pain (PWHpain and PWHnopain, respectively), and people without HIV and pain (Ctrl). Fourteen PWHpain (age, mean ± SD: 59 ± 6.5, 12 males), 13 PWHnopain (55 ± 9, 12 males), and 14 Ctrl (58 ± 10, 14 males) completed a 3T 1 H-magnetic resonance spectroscopy MEGA-PRESS scan quantifying GABA and Glx in the left posterior insula. Furthermore, temporal summation was evaluated using cuff pain algometry, applied on the participants' left calf for 120 seconds at a pressure calibrated to a subjective target pain rating of 40/100. In addition, we evaluated blood plasma levels of neurosteroids (ie, allopregnanolone) known to be endogenous modulators of GABA-A receptors. People with HIV with neuropathic pain exhibited increased temporal summation of cuff pain and decreased posterior insula GABA levels compared to Ctrl and PWHnopain ( P 's < 0.05). There were no statistically significant group differences in Glx. Lower GABA levels were associated with higher average cuff pain ratings (R = -0.44, P < 0.05) and temporal summation scores (R = -0.49, P < 0.01) in PWH. In addition, lower allopregnanolone levels were associated with higher insular Glx levels in PWHpain (R = -0.64, P < 0.05). Our results provide a link between decreased GABA levels and neuropathic pain in PWHpain. These results suggest that insufficient inhibitory metabolite levels, rather than excessive excitatory metabolite levels, may be linked to neuropathic pain in PWH.

Duke Scholars

Author Jason David Kilts Psychiatry, Child & Family Mental Health & Community Psychia ...

Author Christine Elizabeth Marx Psychiatry, Child & Family Mental Health & Community Psychia ...