An evidence-based review of CGRP mechanisms in the propagation of chronic visceral pain

A Pharmacological Review of Calcitonin Gene-Related Peptide Biologics and Future Use for Chronic Pain

“…Central sensitization is a phenomenon by which, at the molecular level, the threshold to propagate action potentials is lowered and less stimuli is needed to transduce a signal to the brain. In relation to pain, we can categorize this as hyperalgesia or allodynia [ 11 ]. Hyperalgesia is a state in which a pain-inducing stimuli produce a greater than expected pain response, while allodynia is a state in which pain is experienced by a stimulus that would not normally elicit pain.…”

“…CGRP has been noted to have a prominent role in this phenomenon, and we will discuss this mechanism of action here. Normally, in a pain response, a stimulus causes an action potential to be sent to the posterior gray column of the spinal cord by afferent nerve fibers [ 11 ]. Here, the primary nerve fibers synapse with second-order neurons in the dorsal horn, causing CGRP, glutamate, SP, and other neuromodulators to be released, which stimulate the second-order neurons, causing an opening of calcium and sodium channels [ 30 ].…”

“…This leads to the generation of an action potential that propagates to the thalamus through the spinothalamic tract producing the sensation of pain [ 31 ]. Continuous stimulation of the dorsal horn may result in central sensitization, leading to the sustained sensation of pain in the context of chronic pain [ 11 ]. This sensitization and sustained activation of the afferent pathway is primarily dependent on the activation of the N-methyl-d-aspartate (NMDA) receptors of the postsynaptic neurons [ 6 ].…”

“…As the primary afferent signal is transduced, it reaches a postsynaptic neuron, which activates the NMDA receptor. This receptor causes the release of nitric oxide (NO), prostaglandin E2, and glutamate, which act in a retrograde fashion to promote the further release of excitatory neurotransmitters from the nerve terminals of the primary afferents, thus maintaining a sensitized state [ 6 , 11 ]. It is worth noting that both an increase in excitatory transmitters and a lower threshold are required to achieve signal transduction.…”

“…The future of CGRP therapy is promising in the treatment of many pathologies. Due to the ubiquitous involvement of CGRP in the human body and the already established treatment regimen for migraines, we suggest that the next logical leap for CGRP therapy may be to expand its use for the treatment of chronic visceral and somatic pain [9][10][11].…”