Pharmacology of visceral pain: central factors.
Clinically, pain can be sub-classified into superficial, neuropathic and deep pain. Deep pain as a result of stimulation to structures such as the viscera is the most poorly understood and notoriously difficult to treat. The dorsal horn of the spinal cord is the gateway to conscious nociception and it is at this point in the pain processing pathway that the peripheral afferent input can be enhanced or inhibited by several mechanisms, the most important being central sensitisation. Long-term potentiation, another mechanism, can also be elicited in the spinal cord. Here nociceptor activity and/or peripheral tissue inflammation produces long-term changes in synaptic efficacy in the dorsal horns. This plays a major role in the generation of acute post-operative and post-traumatic pain, migraine and neuropathic pain. Behavioural consequences of central sensitisation can even be readily detected in human psychophysical experiments. Another important mechanism is 'wind-up', a form of homosynaptic activity-dependent plasticity characterised by a progressive increase in action potential output from dorsal horn neurones. There is an extensive body of literature which has highlighted the importance of central sensitisation. This review examines some of the most significant recent findings with regards to future pharmacology. As we are beginning to understand some of the mechanisms of central sensitisation and its importance in visceral pain, novel receptor sites have been identified, offering exciting possibilities with regards to future pharmacological development not only to visceral pain, but for pain management as a whole.
Aziz
Q
Q
Neurogastroenterology Group, Centre for Digestive Diseases, Blizzard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. q.aziz@qmul.ac.uk
Botha
C
C
Willert
R
R
D000818:Animals; D005767:Gastrointestinal Diseases / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D009473:Neuronal Plasticity / Q000502:physiology; D010146:Pain / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D010812:Physical Stimulation; D013116:Spinal Cord / Q000503:physiopathology; D014781:Viscera / Q000473:pathology* / Q000503:physiopathology