Abstract
Effective and safe pain management in the elderly is a major medical challenge. Furthermore, little is known regarding the effect of aging on nociceptor (pain‐sensing neuron) responsiveness or the function of opioid receptors expressed on nociceptors. Here, we compared the effects of the sensitizing agent, bradykinin (BK), and delta and kappa opioid receptor (DOR, KOR) agonists on nociceptors in young (4‐months‐old) and aged (26‐months‐old) Fisher x Brown Norway rats. Behavioral responses to noxious heat, cold, or mechanical stimulation were determined following intraplantar injections of BK. For all three stimuli, aged rats had a greater allodynic response to BK. In primary cultures, activation of phospholipase C in nociceptors from aged rats was more sensitive to BK than those from young rats. In addition, both opioid agonists, SNC80 (DOR) and Salvinorin A (KOR), produced greater antinociceptive effects in aged rats compared to young rats. Similarly, opioid receptor‐mediated inhibition of adenylyl cyclase activity was greater in nociceptors from aged rats. Overall, our results indicate that aging enhances allodynic effects of the inflammatory mediator, BK, as well as increases antinociceptive effects of opioid agonists. We propose that peripherally‐restricted opioids may be a valuable analgesic strategy for treating pain in the elderly.Grant Funding Source: Supported by T32DA031115, Baptist Health Foundation, Nathan Shock Center of Excellence AG013319
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