PAIN-PERIPHERAL SENSITIZATION

SUMMARY

1. Injury produces peripheral inflammatory response, key constituents include: bradykinin, H⁺ ions, ATP, purines, prostaglandin E2, leukotrienes, cytokines and nerve growth factor (NGF).

2. NGF released by activated macrophages, acts directly upon peptidergic C-fibres expressing the TrkA receptor and is a key component of peripheral sensitization; NGF-TrkA interaction results in intracellular phosphorylation of TRPV1 and rapid development of thermal hyperalgesia.

3. Similar mechanisms may contribute to mechanical hyperalgesia.

4. NGF, once bound to the TrkA receptor is internalized and translocated by retrograde axonal transport to the DRG resulting in enhanced gene expression and increased or novel synthesis of substance P, TRPV1 and Nav1.8 contributing to a delayed enhancement of peripheral nociceptor function.

5. Cytokine inhibitors form the basis of rheumatological DMARD therapy and markedly reduce pain & hyperalgesia in RA.

Reference(s)

Hudspith, M.J. (2019). Anatomy, physiology and pharmacology of pain. Anaesthesia & Intensive Care Medicine, 20(8), pp.419–425. doi:https://doi.org/10.1016/j.mpaic.2019.05.008.

Cifu, D.X. (2020). Braddom’s physical medicine and rehabilitation. Elsevier. Get it on Amazon.
Cuccurullo, S. (2019). Physical medicine and rehabilitation board review. New York: Demosmedical. Get it on Amazon.
O’Young, B., Young, M.A. and Stiens, S.A. (2008). Physical Medicine and Rehabilitation Secrets. Mosby. Get it on Amazon.