My question in biochemistry is “what signals are synthesized in response to pain, and how are they eliminated after the response is no longer needed?”
Perhaps the most widely known such substances secreted in response to pain are endorphins or naturally produced morphine. A recent study showed that the body synthesizes these endogenous opioids in order to increase the body’s pain threshold1. This signal helps the body cope with pain during times of immense stress such as during exercise. Often, this causes a kind of “runner’s high” and helps athletes compete and perform. Morphine binds to opioid receptors, which mediates various cellular responses. Among these are pain relief, sedation, euphoria, and antidepressant effects2. As morphine is a well-studied addictive drug, its elimination from the body is well known. They are first oxidized by the cytochrome P450 enzymes. Then the molecules undergo glucuronidation, which is catalyzed by the enzyme uridine diphosphate glucuronosyltransferase. The molecules then become highly hydrophilic and easily excreted in the urine3.
Another well studied class of molecule synthesized in response to pain is the prostaglandins. These lipid molecules have a wide range of hormone-like effects. Prostaglandins are comprised of twenty carbon molecules and can act as autocrine or paracrine signals. While prostaglandins are mostly studied with respect to vasodilation, constriction, and inflammation, it is well known that they can sensitize spinal neurons to pain. This occurs by reducing synaptic inhibition4. These molecules are also key players in responses such as inflammation, fever, labor, and blood clotting. As they are lipids, they are degraded by lipases. Furthermore, prostaglandin synthases and cyclooxygenases, which synthesize these molecules, can be degraded by ubiquitin mediated protease degradation.
- Nuseir KQ, Alzoubi KH, Alabwaini J, Khabour OF, Kassab MI. Sucrose-induced analgesia during early life modulates adulthood learning and memory formation. Physiol Behav. 2015;145:84-90.
- Shoaib M, Shah SW, Ali N, et al. Scientific investigation of crude alkaloids from medicinal plants for the management of pain. BMC Complement Altern Med. 2016;16(1):178.
- Smith, Howard S. “Opioid Metabolism”. Mayo Clinic Proceedings 84.7 (2009): 613-624. Web. 16 June 2016.
- Reinold H, et al. Spinal inflammatory hyperalgesia is mediated by prostaglandin E receptors of the EP2 subtype. J Clin Invest. 2005;115(3):673–679.