Catalyst Awardee

Project Description

p75 Neurotrophin Receptors in Forebrain Medial Septum Mediate the Enhanced Experimental Chronic Pain in Aged Rodent?

Sanjay Khanna, M.Sc., Ph.D., and Low Chian Ming, M.Sc., Ph.D., National University of Singapore

Competition Sponsor: Ministry of Health and National Research Foundation of Singapore

This proposal tests the hypothesis that the p75 neurotrophin receptors (NTR) in the forebrain medial septum (MS) is a basis of increased chronic pain in aged rodent. Chronic pain affects about 20% of the world population and is debilitating, especially in aged. Indeed, chronic pain is co-morbid with depression, anxiety and cognitive decline and thus affects the lifestyle of patients. Aged rodents, as with humans show enhanced pain on injury in comparison to young. Preliminary experiments from the laboratory suggests that blocking the function of p75 NTR in MS reverses experimental pain due to neuropathy in young rat. However, the role of septal p75 NTR in mediation and enhancement of chronic pain in aged remains unclear. Interestingly, the expression of p75 NTR increases in brain of the aged. Using rodent models, behaviour and cell biology techniques, the proposal will examine (a) the changes in expression of p75 NTR, specifically in MS with age, and (b) the effect of functional antagonism of septal p75 NTR on chronic experimental pain. The function of p75 NTR will be antagonized either with knockdown of the receptor or by microinjection of drugs that antagonize the function of the NTR by binding to it. A demonstration that antagonism of septal p75 NTR effectively blocks pain in aged will be very novel and will be a precursor to a wider investigation into the role of the septal receptor as a common target mediating changes in emotion-motivation in aged of which enhanced chronic pain is one manifestation.

To learn more about this proposal, email healthylongevity@nas.edu.

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