ABSTRACT
We investigated the effect of the prosaposin-derived peptide prosaptide TX14(A) on tactile allodynia in rats following intraplantar injection of the HIV envelope glycoprotein gp120. Systemic administration of TX14(A) dose-dependently prevented onset of tactile allodynia following intraplantar injection of gp120 and also transiently alleviated established allodynia in the same model. TX14(A) did not prevent tactile allodynia when injected directly into the foot pad whereas intrathecal administration of TX14(A) both prevented and alleviated gp120-induced tactile allodynia. Nerve and spinal cord levels of TNFalpha protein were unchanged in intraplantar gp120 injected rats that displayed allodynia. These results indicate that TX14(A) has anti-allodynic properties in a rat model of gp120-induced tactile allodynia and that the mechanism of action of TX14(A) may include modulation of spinal nociceptive processing.
Subject(s)
HIV Envelope Protein gp120 , Hyperalgesia/chemically induced , Hyperalgesia/physiopathology , Nerve Growth Factors/pharmacology , Pain Threshold/drug effects , Animals , Dose-Response Relationship, Drug , Female , Foot , HIV Envelope Protein gp120/administration & dosage , Injections , Injections, Spinal , Nerve Growth Factors/administration & dosage , Rats , Rats, Sprague-Dawley , TouchABSTRACT
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.
