prosaptide and Pain

To examine the efficacy and safety of Prosaptide (PRO) for the treatment of painful HIV-associated sensory neuropathies (HIV-SN).. A randomized, double-blind, placebo-controlled, multicenter study in participants with sensory neuropathy. Pain modulating therapy was discontinued prior to baseline. Participants were stratified by sural sensory nerve action potential (SNAP) amplitude. Participants were trained to use an electronic diary (ED) to record pain.. Peripheral neuropathies are common complications of HIV infection. The pathogenesis is unknown and currently treatments are restricted to symptomatic measures. We examined PRO against placebo (PBO) for treatment of painful HIV-SN and performed a post-hoc evaluation of an electronic diary (ED) to record HIV-associated neuropathic pain.. Eligible participants included adults with neurologist-confirmed painful HIV-SN.. 2, 4, 8, or 16 mg/d PRO or PBO administered via subcutaneous (SC) injection for six weeks. Neurotoxic antiretroviral drug usage was held constant.. Changes from baseline in the weekly average of evaluable daily random prompts measuring pain using the Gracely pain scale and adverse events.. 237 participants were randomized. The study was stopped after a planned futility analysis. There were no between-group differences in the frequency of adverse events or laboratory toxicities. The 6-week mean (sd) Gracely pain scale changes were -0.12 (0.23), -0.24 (0.35), -0.15 (0.32), -0.18 (0.34), and -0.18 (0.32) for the 2, 4, 8, 16 mg, and PBO arms respectively. A similar variability of pain changes recorded using the ED were noted compared to previous trials that used paper collection methods.. 6-week treatment with PRO was safe but not effective at reducing HIV-associated neuropathic pain. Use of an ED to record neuropathic pain is novel in HIV-SN, resulted in reasonable compliance in recording pain data, but did not decrease the variability of pain scores compared to historical paper collection methods.. Current Controlled Trials NCT00286377.

Topics: Adult; Computers, Handheld; Double-Blind Method; Female; HIV; HIV Infections; Humans; Male; Medical Records Systems, Computerized; Nerve Growth Factors; Pain; Placebos; Polyneuropathies; Prospective Studies; Treatment Outcome

We have previously demonstrated that the prosaposin-derived 14-mer peptide TX14(A) prevents structural and functional abnormalities associated with peripheral neuropathy in diabetic rats. Unusually, this neuroprotective peptide also exhibited acute anti-hyperalgesic properties in the same model, suggesting a dual action of TX14(A) that could allow therapeutic targeting of both degenerative neuropathy and neuropathic pain. In the present study, we have extended investigation of the anti-allodynic properties of TX14(A) to a range of models in which allodynia is induced using metabolic, physical, neurotoxic or chemical/inflammatory damage to the peripheral nerve. Single systemic doses of TX14(A) rapidly alleviated tactile allodynia in rats in which nerve injury was induced by diabetes, sciatic nerve hemiligation, systemic paclitaxel treatment or paw formalin injection. Further, TX14(A) pre-treatment prevented onset of allodynia in the paclitaxel and formalin injection models. These results indicate that TX14(A) has anti-allodynic properties in diverse models of neuropathic pain and support further exploration of its potential as a therapeutic agent for a wide range of peripheral neuropathies and neuropathic pain states.

Topics: Analgesics, Non-Narcotic; Analysis of Variance; Animals; Diabetes Complications; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Nerve Growth Factors; Paclitaxel; Pain; Pain Measurement; Pain Threshold; Rats; Rats, Sprague-Dawley; Sciatica; Skin; Time Factors