Pathophysiology & Clinical Implications


Pain Pathophysiology: Pain has a biologically important protective function. The sensation of pain is a normal response to injury or disease and is a result of normal physiological processes within the nociceptive system, with its complex of stages previously described. There may also be other manifestations of pain related to tissue injury including hyperalgesia, an exaggerated response to a noxious stimulus, and allodynia, the perception of pain from normally innocuous stimuli. Hyperalgesia and allodynia are the result of changes in either the peripheral or central nervous systems, referred to as peripheral or central sensitization, respectively.

Genetic and environmental factors contribute to sensitization resulting in persistent (chronic) pain in some individuals even after healing has taken place. Nociceptors not only signal acute pain, but when chronically sensitized, contribute to persistent pathological pain disorders from previous injury or ongoing disease. Chronic pain is also characterized by the abnormal state and function of the spinal cord neurons which become hyperactive. This hyperactivity is the result of increased transmitter release by spontaneously active primary afferent neurons and an increased responsiveness of postsynaptic receptors (in part due to phosphorylation of glutamate-activated NMDA receptors). A hyperexcitable state of synaptic transmission at the dorsal horn is further maintained by release of biologically active factors from activated glia. The state of hyperexcitability is aggravated by the loss of inhibitory interneurons involved in the modulation of pain.

Under normal circumstances the nociceptive sensory system returns to a normal functional state as soon as healing takes place. But many features of sensitization persist and are manifest as chronic pain and hyperalgesia, especially when the nervous system itself is injured leading to chronic neuropathic pain. Imaging studies have shown that chronic pain is accompanied by permanent structural alterations in specific brain areas that play a crucial role in nociception.

 Implication for Clinical Practice 

Treatment should aim to decrease the intensity of acute pain in an effort to reduce or prevent permanent changes in the nervous system that may result in chronic pain. Multimodal therapy which involves drug and non-drug treatments and rational combinations of drugs that work by different mechanisms are important in providing optimal relief of pain and reducing the probability of persistent changes that characterize chronic pain.