Therapeutic efficacy of prosaposin-derived peptide on different models of allodynia.
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.
Department of Pathology, University of California San Diego, USA. cjolivalt@ucsd.edu
Corinne G
CG
Jolivalt
Khara M
KM
Ramos
Katrin
K
Herbetsson
Fred S
FS
Esch
Nigel A
NA
Calcutt
D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D048909:Diabetes Complications / Q000150:complications; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D009414:Nerve Growth Factors / Q000627:therapeutic use*; D017239:Paclitaxel / Q000009:adverse effects; D010146:Pain / Q000188:drug therapy* / Q000209:etiology*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012585:Sciatica / Q000150:complications / Q000188:drug therapy; D012867:Skin / Q000294:innervation*; D013997:Time Factors
D018712:Analgesics, Non-Narcotic; D009414:Nerve Growth Factors; C101246:prosaptide; D017239:Paclitaxel