Annals ofthe Rheumatic Diseases 1996; 55: 411-420 41 REVIEW: PAIN Series editor: Bruce L Kidd Ann Rheum Dis: first published as 10.1136/ard.55.7.411 on 1 July 1996. Downloaded from Cerebral mechanisms operating in the presence and absence of inflammatory pain Anthony K P Jones, Stuart W G Derbyshire During episodes ofinflammatory arthritic pain, surprising if such parallel processing did not the brain has the task of integrating new also exist for non-primary sensations such as information from receptors of muscle, tendon, pain. There is now growing evidence that pain and skin afferents with nociceptive information is processed by a network or 'matrix' of struc- from the joint capsule and, possibly, peri- tures in the brain (fig 1), some components of articular bone. This integration will incorpor- which could be considered to comprise parallel ate motivational, affective, discriminative, at- but integrated processing. tentional, and motor responses that may result in changes of behaviour and modification of central nervous system (CNS) processing of NEUROANATOMY OF NOCICEPTION IN ANIMALS pain. It is as yet unclear what the nature of this Studying pain in animals presents an insoluble CNS modification may be, and suggested problem. Human beings can call out and influences on pain related affective-motor express their pain in ways that are commonly responses or the inflammatory process itself understandable to other members of their remain largely speculative. species; unfortunately, there is no equivalent It is likely to be some time before we begin frame of reference when dealing with animals. to have a proper understanding of the complex Increased blood pressure, movements of integrated processes that operate during withdrawal, dilatation of the pupil, increased arthritic pain and other chronic pains. How- depth of ventilation, attacking the source of ever, we are now able to measure aspects of noxious stimulation, and cries may be common those processes in terms of measurement of to all mammals in the face of seemingly 'pain- behavioural and cerebral responses to pain. ful' stimulation, but all such responses can be These measurements are providing early clues elicited after the cerebral cortex has been to the possible underlying CNS mechanisms destroyed, in the probable absence of any and their relation to changes in affective- subjective experience. Furthermore, the sub- http://ard.bmj.com/ motivational behaviour. This paper will review jective experiences of an animal, if it has any, the normal brain mechanisms of the conscious may be totally different from those of humans. appreciation of pain, together with working For these reasons, human interpretation of hypotheses for how these mechanisms are what is observed in another species cannot be altered during inflammatory and other types of by extrapolation from human experience. clinical pain syndromes. This is not to suggest that all 'pain' research in animals is valueless: the common ancestry on October 1, 2021 by guest. Protected copyright. between humans and animals suggests that Normal mechanisms: anatomy and some of the underlying biological processes physiology involved in human pain experience are likely to It is perhaps surprising that there should still be shared with other animals. A distinction is be debate about which areas of the brain might therefore drawn between 'nociception' and be involved in the processing of such an pain-which should not be used inter- important and commonplace sensation as pain. changeably-the term nociception being used This has come about largely because of the to refer to the biological response of receptors understanding of pain as an experience involv- in tissue to potentially damaging stimuli such ing sensory, cognitive-evaluative, and affective- as intense heat or cold, chemical irritation, or motivational components' which defies simple intense pressure. The study ofnociceptive pain explanations involving pain centres' and avoids the fact that pain in man can occur Human Physiology and specific pathways.2 without any evident nociceptor activation, as in Pain Research Whatever areas of the brain are involved in peripheral and central deafferentation pain, Laboratory, of the different Manchester University pain processing, integration and may also occur without any evidence of Rheumatic Diseases components must be accommodated. This spinothalamic tract activation, as in psycho- Centre, Clinical implies that there is unlikely to be any final genic pain. Sciences Building, common area of the brain that processes pain. The spinothalamic tract has been demon- Hope Hospital, Salford M6 8HD, Indeed, it is perhaps the search for a single strated to be 'both necessary and sufficient' for United Kingdom dominant 'pain centre' that has done more to nociception in most species studied.4 It pro- A K P Jones impair our understanding of the functional vides the major direct nociceptive input from S W G Derbyshire anatomy of pain than anything else. Parallel the spinal cord to the thalamus. As a conse- Correspondence to: Dr Jones. processing of the conscious appreciation of quence, the spinothalamic tract ascending in Accepted for publication primary sensations such as vision and touch3 the anterolateral cord is widely considered as 14 March 1996 are now well documented, and it would be the 'pain pathway'. 412 Jones, Derbyshire Spinothalamic tracts The cortical projections of the thalamic In the early 19th century, Brown-Sequard nuclear terminations of the dorsal and ventral performed studies in which the ventrolateral spinothalamic tracts are not clearly defined in quadrants of the spinal cord were sectioned in any species. Although the cortical connections Ann Rheum Dis: first published as 10.1136/ard.55.7.411 on 1 July 1996. Downloaded from animals and the resulting effects compared of some of the more important nuclei have with sensory deficits caused by similar lesions been described in different species, it cannot be in humans.5 Sherrington and Laslett6 observed assumed that all these connections are necess- 'that the lateral column furnishes the headward arily relevant to the spinothalamic termin- path in the spinal cord for nociceptive (algesic) ations. The following descriptions of cortical arcs' and 'that this is true for these arcs, projections can only therefore be a pointer to whether they are traced from skin, muscle or some of the possible functional connections in viscera'. Lesioning of the ventral quadrant in relation to the spinothalamic tracts. monkeys results in a consistent increase in Both components ofthe spinothalamic tracts response thresholds to nociceptive stimuli on have a heavy projection to the caudal portion the contralateral side below the level of the of the ventral posterior lateral nucleus of the lesion.7 8 This analgesic response usually re- thalamus. This nucleus, in addition to the covers one to six months after the lesioning.9 ventral posterior inferior and the centrolateral The most long lasting analgesic effects were nuclei of the thalamus, have important pro- produced by the most extensive lesions includ- jections to neurones in the primary somato- ing both dorsal and ventral quadrants, indicat- sensory cortex (SI) which are probably noci- ing that other pathways may also transmit noci- ceptive.'3 There are also probable nociceptive ceptive information, or that the spinothalamic projections from thalamic nuclei (ventral tract may have important dorsal components. posterior lateral, posterior nucleus, and the Quantitative studies also have demonstrated an centrolateral nucleus) to the secondary important contribution of the dorsolateral fasci- somatosensory cortex (S2). ' Although it has culus to the spinothalamic tract.'0 The thalamus been shown that SI contains units that respond was injected with agglutinin conjugated horse- to noxious stimuli,'5 Shi et al'3 have argued that radish peroxidase (HRP) in the presence and 'nociception does not seem to be a sensory absence of thoracic spinal lesions to preserve modality that is prominently represented in either the ipsilateral or contralateral ventral either the first or the second somatic sensory quadrant or dorsolateral fasciculus: 25-30% of area of the parietal cortex. Since the terminals the cells staining for HRP in the lumbar of the [spinothalamic tract] are scattered in segments were accounted for by retrograde small patches, since the cortical projections transport of stain down the contralateral dorso- from the VPLC (caudal section of the ventral lateral tract. These authors also found signifi- posterior lateral nucleus) are restricted to small cant differences in the distributions of cells of areas,'6 since VPLC cells in a given somatotopic origin of these two pathways. The most striking area project to multiple cortical zones and not observation was the predominance of laminae all VPLC cells project to the cortext'7. ..'. http://ard.bmj.com/ I-III of the dorsal horn as the main sites of The pulvinar oralis and the suprageniculate origin of the dorsolateral funiculus and laminae nucleus have been termed the posterior region VII-X as the main sites of origin of the ventral of the thalamus, and this region receives over- quadrant of the spinothalamic tract. Laminae lapping terminations from both spinothalamic IV-VI made a variable and often significant components. This area in turn projects to the contribution, dependent on the species of insular cortices in primates'8 which, because of monkey. An ipsilateral origin was demonstrated its