Descending, propriospinal, and segmental modulatory systems, tonically or phasically inhibit or facilitate the spinal transmission of nociceptive signals. Although it is widely accepted that these endogenous modulatory systems affect sensations of pain, the way in which they are brought into play and their consequences on nociceptive behaviour have rarely been addressed in the context of tissue injury. An increase of tonic descending modulation has been demonstrated during the acute stage of inflammation in both electrophysiological and behavioural experiments suggesting that this enhanced descending inhibition may limit hyperalgesia during acute inflammation.1
To analyse further the changes of pain modulatory systems under pathological conditions and determine their potential role in the pathophysiology of pain syndromes, we investigated in a recent series of electrophysiological studies in the rat the modulation of the spinal transmission of nociceptive information during the course of inflammation.
In a first series of experiments,2 diffuse noxious inhibitory controls (DNIC), which are supraspinally mediated inhibitory controls triggered by the application of noxious stimuli, were investigated at different stages during the development of adjuvant-induced monoarthritis in the rat. In the acute stage of monoarthritis (i.e., 24–48 h), the DNIC-induced inhibitions of nociceptive neurons produced by mechanical or thermal stimulation of the arthritic joint were significantly increased at all intensities by comparison with the normal joint. In contrast, in the animals with a chronic monoarthritis (i.e., 3–4 weeks), the DNIC-induced inhibitions were not different from those observed in control animals. These data suggested that chronic inflammatory processes might have induced a reorganisation of the spinal transmission of nociceptive signals and/or modulatory systems, which could modify the recruitment of DNIC.
To test these hypotheses, other experiments were designed to analyse the changes of tonic modulation acting on the spinal transmission of nociceptive information in rats with acute or chronic monoarthritis.3 Tonic descending inhibitions were analysed by comparing the electrophysiological properties of spinal convergent neurons with ankle input before and after spinalization. Tonic descending inhibition of convergent neurons with input from the inflamed ankle was enhanced during the acute stage and then decreased during the chronic stage of monoarthritis. In addition, changes in the spinal transmission of nociceptive signals were unmasked by removing descending modulation in animals with monoarthritis: sensitisation of spinal neurons with input from the inflamed ankle was demonstrated during the acute stage of monoarthritis, while a crossed transmission between inflamed and normal sides was observed during the chronic stage of the disease.
In conclusion, these studies showed dynamic and stage-dependent modifications of the spinal transmission and modulation of nociceptive information during the course of inflammation. During both acute and chronic stages of inflammation, descending controls tended to dampen central changes at the spinal level. Such a functional plasticity might play a significant role in the pathophysiology of some acute or chronic pain syndromes observed in humans: an imbalance of descending controls could exacerbate the consequences of the central changes induced by the inflammatory processes and could result in increased and persistent pain.
Dubner R, Ren K. Endogenous mechanisms of sensory modulation. Pain Suppl. 1999;6:S45
Danziger N, Weil-Fugazza J, Le Bars D, Bouhassira D. Alteration of descending modulation of nociception during the course of monoarthritis in the rat. J Neurosci. 1999;19:2394–2400
Danziger N, Weil-Fugazza J, Le Bars D, Bouhassira D. Stage-dependent changes in the modulation of spinal nociceptive neuronal activity during the course of inflammation. Eur J Neurosci. 2001;13:230–40
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