Pain Trials—Are We Measuring the Wrong Response?

New insights into pain pathways suggest that existing approaches to assessing the efficacy of novel compounds for pain may be flawed, leading to the discounting of possibly effective candidates. A research team led by investigators from Harvard Medical School reports that it has identified the nerve signaling pathway associated with sustained pain following an injury, and how it differs from the signaling path that triggers a reflexive response to the injury itself. By focusing on measurement of this initial, tissue-saving response, rather than on the extent of the lasting pain sensation, the authors assert that experiments on new drug compounds might be discounting some that are actually viable alternatives for pain management. Senior author Qiufu Ma, PhD, professor of neurobiology in the Blavatnik Institute at Harvard Medical School, remarked, “The ongoing opioid crisis has created an acute and pressing need to develop new pain treatments, and our findings suggest that a more tailored approach to assessing pain response would be to focus on sustained pain response rather than reflexive protective withdrawal.” The findings were published earlier this week in the journal Nature.

Working with mouse models, the team identified the different signaling pathways that are associated with a reflexive withdrawal response to a paw injury vs a pain alleviating response (paw-licking) following the injury. 2 sets of neurons, Tac1, located in the dorsal horn, and Trpv1, dispersed throughout the body, were identified as responsible for the transmission of postinjury pain signals. Dr. Ma commented, “We believe that Tac1 neurons act as a relay station that dispatches pain signals from the tissue, through Trpv1 nerve fibers all the way to the brain,” adding, with respect to the implications for pain trials, “All these years, researchers may have been measuring the wrong response. Indeed, our results could explain, at least in part, the poor translation of candidate treatments from preclinical studies into effective pain therapies.”

Read about the study.

The journal abstract may be read here.