Understanding Neuropathic Pain (NeP)
The Pain Response and Sensitisation
Pain is normally produced by intense stimuli that help to protect us by causing us to withdraw from noxious stimuli that are actually or potentially damaging to tissues.1 Nociceptive pain is therefore an early warning device that protects individuals from harm in a dangerous environment. Clinical pain, in contrast, results from damage to tissue and inflammation, damage to the nervous system, and alterations in the normal functioning of the nervous system. Clinical pain consists of both spontaneous pain that may arise with no apparent peripheral stimulus, and from hypersensitivity to peripheral stimuli.2 Pain hypersensitivity may persist long after an injury has healed or may be seen in the absence of injury.3
Two mechanisms are involved:
- Peripheral sensitisation: reduction in threshold and increase in responsiveness of the peripheral ends of nociceptors.1,2
- Central sensitisation: increased excitability of CNS neurons.1,2
Peripheral sensitisation contributes to the pain hypersensitivity at sites of tissue damage and inflammation. An example is the change in heat sensitivity after sunburn. The sensitisation is produced by the action of inflammatory chemicals and/or mediators released around the site of tissue damage. This increases the responsiveness of peripheral nociceptors, and can be attenuated by drugs such as aspirin and anti-inflammatory pain killers.4
The increased excitability in central sensitisation is typically triggered by a burst of activity in nociceptors (such as that evoked by an injury) which alter the strength of synaptic connections between the nociceptor and the neurons of the spinal cord (so-called activity-dependent synaptic plasticity). As a result, an input that would normally evoke an innocuous sensation now produces pain. Although the pain feels as if it originates in the periphery, it is actually caused by abnormal sensory processing within the CNS.2 This is known as wind-up and is discussed further in the mechanism of neuropathic pain section.
