Research in mice identifies a set of neurons responsible for sustained pain and resulting pain-coping behaviors Findings point to the existence of separate neural pathways that regulate threat avoidance versus injury mitigation Study can inform new ways to gauge the efficacy of candidate pain therapies by assessing behaviors stemming from different pathways.
Withdrawing one's hand to avoid injury and soothing the pain of that injury are two distinct evolutionary responses, but their molecular origins and signaling pathways have eluded scientists thus far.
Now research led by investigators at Harvard Medical School identifies the nerve-signaling pathway behind the deep, sustained pain that sets in immediately following injury. The findings also shed light on the different pathways that drive reflexive withdrawal to avoid injury and the subsequent pain-coping responses.
Clinical observations of patients with neurological damage together with past research have outlined the distinct brain regions that differentiate between the reflexive withdrawal from a skin prick, for example, and the long-lasting pain arising from tissue injury caused by the pinprick.
The new study, however, is the first one to map out how these responses arise outside the brain
The findings, based on experiments in mice, put into question the validity of current experimental approaches for assessing the efficacy of candidate pain-relief compounds. Most current methods rely on measuring the initial, reflexive response that serves to avert tissue injury, rather than on measuring the lasting pain that arises from actual tissue damage, the researchers said. As a result, they said, some drug compounds that might have been successful in assuaging the sustained pain, the lasting sensation of pain that immediately follows injury, could have been dismissed as ineffective because they were assessed against the wrong outcome.
The team focused on a set of neurons called Tac1 emanating from the so-called dorsal horn, a cluster of nerves located at the lower end of the spinal cord that transmit signals between the brain and the rest of the body. The precise function of Tac1 had remained poorly understood so Ma and colleagues wanted to know whether and how these neurons were involved in the sensation of sustained pain.
In a series of experiments, the team assessed pain response in two groups of mice, one with intact Tac1 neurons and another with chemically disabled Tac1 neurons
The results of the study affirm the presence of two lines of defense in response to injury, each controlled by separate nerve-signaling pathways. The rapid withdrawal reflex is nature's first line of defense, an escape attempt designed to avoid injury. By contrast, the secondary, pain coping response helps reduce suffering and avert widespread tissue damage as a result of the injury.