Therapeutic potential for leukocyte elastase in chronic pain states harboring a neuropathic component
نویسندگان
چکیده
Neuropathic pain is an integral component of several chronic pain conditions and poses a major health problem worldwide. Despite emerging understanding of mechanisms behind neuropathic pain, the available treatment options are still limited in efficacy or associated with side effects, therefore making it necessary to find viable alternatives. In a genetic screen, we recently identified SerpinA3N, a serine protease inhibitor secreted in response to nerve damage by the dorsal root ganglion neurons and we showed that SerpinA3N acts against induction of neuropathic pain by inhibiting the T-cell- and neutrophil-derived protease, leucocyte elastase (LE). In the current study, via detailed in vivo pharmacology combined with analyses of evoked- and spontaneous pain-related behaviors in mice, we report that on systemic delivery, a single dose of 3 independent LE inhibitors can block established nociceptive hypersensitivity in early and late phases in the spared nerve injury model of traumatic neuropathic pain in mice. We further report the strong efficacy of systemic LE inhibitors in reversing ongoing pain in 2 other clinically relevant mouse models-painful diabetic neuropathy and cancer pain. Detailed immunohistochemical analyses on the peripheral tissue samples revealed that both T-Lymphocytes and neutrophils are the sources of LE on peripheral nerve injury, whereas neutrophils are the primary source of LE in diabetic neuropathic conditions. In summary, our results provide compelling evidence for a strong therapeutic potential of generic LE inhibitors for the treatment of neuropathic pain and other chronic pain conditions harboring a neuropathic pain component.
منابع مشابه
P 33: Effect of Alcoholic Extract of Rosmarinus officinalis L. and Rosmarinic Acid on Inflammation Induced by Chronic Constriction Injury (CCI) Model of Neuropathic Pain in Rats
Introduction: Rosemary, Rosmarinus (R.) officinalis L. is a well-known plant with several useful properties such as analgesic, anti-inflammatory and anti-neurodegenerative. It has been used in folk medicine to alleviate rheumatic pain, stomachache and dysmenorrhea. Rosemary has several constituents such as rosmarinic acid which can be responsible for therapeutic properties been noted with rosem...
متن کاملEffects of combined chronic progesterone administration and forced exercise on behavioral pain responses in the neuropathic pain model of chronic constriction injury in rats
Introduction: Neuropathic pain is a chronic pain that results from damage to the central and peripheral nerves. According to the previous studies, physical activity or progesterone can be an effective treatment for alleviating sensory neuropathic pain individually. In this way, the combined effect of chronic progesterone and forced exercise on behavioral pain responses in the neuropathic pain m...
متن کاملAntinociceptive effects of maprotiline in a rat model of peripheral neuropathic pain: possible involvement of opioid system
Objective(s): Neuropathic pain remains a clinical problem and is poorly relieved by conventional analgesics. This study was designed to determine whether maprotiline administration was effective in alleviating symptoms of neuropathic pain and whether the antinociceptive effect of maprotiline mediated through the opioid system. Materials and Methods: Neuropathic pain was induced by chronic cons...
متن کاملEffects of co-administration of chronic curcumin and forced exercise on behavioral pain responses in the neuropathic pain model of chronic constriction injury in rats
Introduction: Neuropathic pain is a chronic pain that results from damage to the central and peripheral nerves. According to the previous studies, curcumin and exercise can be effective treatments for alleviating sensory neuropathic pain individually. Now the combined effect of chronic curcumin (Cur) and forced exercise on behavioral pain responses in the neuropathic pain model of chronic const...
متن کاملIntrathecal transplantation of cultured calf chromaffin cells attenuate sensory motor dysfunction in a rat model of neuropathic pain
The potential usefulness of chromaffin cells as a source of neuroactive agents for transplantation in the CNS is based on several promising features, including the diversity of biologically active neurotransmitters, neuropeptides and trophic factors produced by the cells. The purpose of this study was to test the possibility that motor as well as sensory dysfunction is reduced by cultured chrom...
متن کامل