This application addresses the critical need for efficacious non-pharmacological treatments for human
immunodeficiency virus type 1 (HIV) sensory neuropathy (HIV-SN). This neuropathy can be associated with
viral infection alone, likely involving a role for the envelope glycoprotein gp120; or a drug-induced toxic
neuropathy associated with the use of nucleoside analogue reverse transcriptase inhibitors (NRTIs) as a
component of highly active anti-retroviral therapy. Dr. Mohab Ibrahim, Principal Investigator on this project,
along with Dr. Rajesh Khanna, a co-Investigator on this project, first showed that low intensity green light
provided long-lasting antinociception in naïve animals. No side-effects were noted and motor performance was
not impaired. The antinociception may be due to increased endogenous opioid expression observed in the
spinal cord and possibly the decrease in inflammatory factors. Their recent work also demonstrated reversal of
mechanical and thermal hypersensitivity in rats subjected to spinal nerve ligation– a model of chronic
neuropathic pain. Thus, understanding the mechanisms that contribute to green light mediated antinociception
would be a critical first step in developing this as a novel form of therapy. We will test our hypothesis that
exposure to green light will reduce thermal, mechanical hypersensitivity due to engagement of the
endogenous opioid system and decrease inflammatory mediators. We will test this hypothesis with four
related, but independent, specific aims using the envelope glycoprotein gp120 model of HIV-induced painful
peripheral neuropathy. We will first determine the time-course and light intensity (lux levels) needed for
reversal of thermal and mechanical hypersensitivity in the gp120 model of HIV-induced painful peripheral
neuropathy and the mechanical hypersensitivity associated with antiretroviral therapy (SA1). Next, we will
determine the contribution of the endogenous opioid system in mediating the effects of green light emitting
diode (GLED) and whether a fixed light intensity/duration along with a mu opioid receptor agonist or a non
opioid neuropathic pain medication such as gabapentin result in a synergistic antinociceptive effect in animals
with gp120-induced neuropathy (SA2). We will characterize cellular activation and determine the levels of
inflammatory cytokines in the spinal cord dorsal horn, brain, cerebrospinal fluid, and plasma from rats with
gp120-induced neuropathy and following GLED exposure (SA3). Finally, we will investigate possible side
effects that may be associated with prolonged exposure to green light therapy in preparation for introducing
this therapy to human patients (SA4). Green light therapy resulting in decreased chronic pain without side
effects has the promise of being easily translatable into the clinic due to their apparent efficacy, safety, low cost
and availability. Our studies may offer an adjunct to current clinical therapies likely resulting in reducing
opioids to manage HIV induced neuropathic pain, as well as other chronic pain states. Importantly,
with a reduction in their pain, HIV patients may be more compliant with their antiretroviral therapy.