A review of contralateral responses to a unilateral inflammatory lesion

Autor: E M Roberts, Nigel Harris, Richard C Haigh, P. I. Mapp, D. R. Blake, N. G. Shenker
Rok vydání: 2003
Předmět:
Zdroj: Rheumatology. 42:1279-1286
ISSN: 1460-2172
Popis: Symmetry is a remarkably constant clinical feature of chronic inflammatory disease. Rheumatoid arthritis is almost by definition symmetrical [1]. Osteoarthritis, psoriasis and some of its associated arthritides are also symmetrical [2–4]. Pulmonary fibrosis, glomerulonephritis and sympathetic ophthalmia are also symmetrical inflammatory conditions. Whilst the pathophysiology behind this symmetry is unexplained, we and others have speculated that it is likely to be mediated via neurological mechanisms crossing through the spinal cord [5, 6]. The two sides of the spinal column have largely been thought to function independently of each other. There are three lines of evidence to suggest that this is not true. Careful anatomical studies of the spinal cord show transmedian fibres decussating posteriorly at all levels of the spinal cord to synapse in the laminae on the contralateral dorsal horn. These neuronal connections have been seen in many different species, including several primates (Fig. 1). Szentagothai [7], using Golgi analysis on young cats and dogs, showed that neurons with their cell bodies in the substantia gelatinosa send contralateral axons that appear to synapse in the contralateral substantia gelatinosa. Perl and Light [8] corroborated these findings after they had applied horseradish peroxidase to rat, cat and monkey dorsal rootlets. They found projections into the contralateral substantia gelatinosa as well as the ventral portion of the nucleus propius. Culberson et al. [9], using cresyl violet acetate (Fink-Heimer method), identified crossed afferent projections throughout the spinal cord, originating and terminating in laminae III–IV, in four mammalian species. These anatomical studies provide evidence that the opportunity exists for crosstalk between the left and the right sides of the spinal column. Functional studies of decerebrate rats demonstrate that such cross-communication can produce contralateral responses. Electrical stimulation of contralateral peripheral nerves is known to inhibit flexor reflex pathways in the spinal cord [10] as well as the long latency of C-fibre-evoked activity in dorsal horn cells [11, 12]. Contralateral dorsal horn cells are inhibited in response to noxious stimuli applied to the limb or tails of rats [13, 14]. Further electrophysiological studies confirm the presence of neurons in the dorsal horn that have bilateral receptive fields. Of relevance to this article is that the number of these neurons with bilateral receptive fields increases in the presence of unilateral inflammation [15, 16]. Grubb et al. [17] also showed that some of the fields on the contralateral side can become excitatory rather than inhibitory. At what level are these contralateral responses mediated? Woolf [16] documented the persistent reduction in flexor reflex thresholds contralaterally after noxious thermal stimuli had been applied to decerebrate rats with an intact brainstem. Fitzgerald [18], using a decerebrate, spinalized rat model, showed that a contralateral effect on dorsal horn fibres need not involve such higher pathways. Although direct contralateral spinal pathways exist in experimental conditions, there are likely to be significant supraspinal influences in vivo. This is suggested by several studies detailing an attenuation of central sensitization and secondary hyperalgesia following spinalization or inactivation of the rostral ventral medulla in a review of rat models of acute pain [19].
Databáze: OpenAIRE
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