Peripheral nociception and the genesis of persistent clinical pain

Pain can be divided into two distinct categories, nociceptive and clinical. The detection of, or reaction to damaging or noxious stimuli, the phenomenon of nociception, is mediated in the periphery by highly specialized primary sensory neurons, the nociceptors. These have peripheral terminals that are activated only by high intensity mechanical, thermal and chemical stimuli. Nociceptive pain, the ‘ouch’ pain typically experienced on touching a hot object or stubbing a toe, is the readout from a protective system fundamental to maintaining bodily integrity in a potentially lethal environment. The key physiological role of this system is well illustrated by the tissue destruction produced both in the denervated (Charcot) joints and neuropathic ulcers in diabetic patients, or in the mutilating injuries seen in patients with congenital insensitivity to pain due to a loss of nociceptor sensory neurons during development, as a result of a mutation of the TrkA receptor (Indo et al., 1996).Nociceptive pain contributes to the pain associated with the onset of acute trauma and is amenable to a variety of therapies that directly target the nociceptor neuron. These include blocking input to the spinal cord with local anesthetic nerve blockade, epidural or spinal anesthesia or reducing transmission from the nociceptor to the CNS with high dose opioids.