There are the unfortunate patients who develop pain hypersensitivity. These patients have a pain threshold that is lower than normal, and the duration of the pain response can become long-lived. There are two main mechanisms of pain hypersensitivity: peripheral sensitization and central sensitization. Peripheral sensitization is associated with inflammation and tissue damage, things found in a variety of rheumatic diseases. One notes an increase in the patient’s response to the peripheral ends of nociceptors, which are the nerve cell endings that transmit pain signals to the brain in response to noxious stimuli.
Peripheral sensitization is the result of changes in transduction proteins—the carriers of messages--that affect the excitability of nociceptors. Noxious stimuli, such as excessive heat, are transformed into an electric response in the nervous system via these proteins. Normally, we begin to find heat painful at approximately 108° Fahrenheit, but after peripheral sensitization, that threshold temperature may be much lower. In fact, the threshold may be so low that washing hands in warm water can be excruciating.
In contrast, central sensitization involves an increase in the excitability of neurons in the central nervous system, resulting in patients displaying what appears to be an exaggerated response to seemingly innocuous stimuli. Inflammation and actual damage to tissue are not essential in central sensitization. Conditions that have their origins through central sensitization include fibromyalgia, irritable bowel syndrome, and temporomandibular joint disorder, to name but a few. In central sensitization there appears to be a change in the relationship between the nociceptors that start the journey of pain, and the brain.