Anatomy, physiology and pharmacology of pain
W Paul Farquhar-Smith
Pain • an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such • Has also been described in terms of a psychological and mental experience. although seemingly trite, pain is what the patient says it is Allodynia • Pain due to astimulus that does not normally provoke pain • Clinically mechanical allodynia is tested by stroking with a brush or cotton wool or by punctuate stimuli such as with a von Frey hair. non-noxious sensory stimuli of other modalities (e.g. heat/cold) can also be tested Hyperalgesia • an increased response to a stimulus that is already painful; the consequence of primary and secondary sensitization •Mechanical hyperalgesia is assessed with von Frey hairs (of sufficient strength to provide a painful punctuate stimulus), and thermal hyperalgesia with thermotesting Dysaesthesia • an unpleasant abnormal sensation, whether spontaneous or evoked • Hyperalgesia and allodynia are specific cases of dysaesthesia Hyperaesthesia • increased sensitivity to stimulation, excluding the special senses • Hyperalgesiaand allodynia are specific cases of hyperaesthesia Table 1
although there is an anatomical framework that is involved in pain processing, this system is not ‘hard wired’ but undergoes changes affecting the sensitivity and the ‘gain’ of nociception. Peripheral sensitization contributes to increasing afferent barrage to the spinal cord. it is mediated by many diverse elements,including nerve and immune cells, in a complex array of algogenic products. numerous receptors and ion channels are involved. Continuing increased input into the spinal cord causes further changes of central sensitization. The glutamate receptor, n-methyl-d-aspartate (nMDa) is pivotal to these processes. The nMDa receptor is therefore a potential target for analgesic therapy. Visceral pain shares thefeatures of the pain mechanisms described in this article, but there are some anatomical, physiological and biochemical differences to somatic pain. Damage to nerves causes changes in excitability, which induce similar peripheral and central sensitization processes that contribute to neuropathic pain. Knowledge of all these processes identifies not only a rationale for standard pain treatments butalso novel potential analgesic targets. However, these systems display complex interactions and, rather than targeting a single moiety, a multi-mechanistic approach to analgesia is required.
Keywords cytokines; nerve growth factor; neuropathic; n-methyld-aspartate;
Pain is a singular human experience influenced by diverse ele ments such as emotion, cognition,memory and social constructs. Although it is convenient to frame pain in anatomical, physio logical and pharmacological terms, it should be considered that many other factors are involved and require a multifactorial approach to achieve analgesia (Table 1). Pain can have patho logical consequences, and its control is a treatment imperative (Table 2).
transduced into electrophysiological signalsthat are trans mitted to perceptive apparatus. However, the pain pathway is not ‘hard wired’, but undergoes profound functional changes and modulation under certain conditions, such as tissue dam age and inflammation (e.g. postoperative pain). This plasticity is mediated by many mechanisms, including peripheral/pri mary and central/secondary sensitization. The substrate for these changes is aplethora of chemical mediators peripherally and spinally, comparable in complexity to neurotransmitters in the brain. Anatomical classification of nociceptors: specialized detectors (nociceptors) respond to noxious stimuli of many modalities, including thermal, chemical and mechanical. Somatic noci ceptors have been classified according to anatomical features and physiological characteristics....