Mechanisms of Referred Trophic Changes

The areas of referred pain/hyperalgesia are frequently the sites of referred trophic changes, as already reported above. If the hyperalgesic state can be explained by central mechanisms, it is difficult to postulate a similar mechanism for the occurrence of objective changes in the periphery. Thus alternative mechanisms need to be hypothesized. Regarding changes in muscle, one hypothesis is a reflex arc activation involving sensory fibers from the internal organ, as the afferent branch of the reflex, and somatic efferents to the skeletal muscle, as the efferent branch of the reflex. This mechanism has been postulated based on the clinical observation that the area of pain referral from viscera is often the site of sustained muscle contraction (2,22); the activation of somatic efferents would thus produce sustained contraction in the skeletal muscle, the first possible step toward a dystrophic reaction of the tissue. The muscle contraction could also contribute to the hypersensitivity via sensitization of nociceptors locally. A recent study in the rat model of referred muscle hyperalgesia from artificial ureteric calculosis has indeed provided some experimental support for this so far hypothetical mechanism. Positivity was found for a number of ultrastructural indices of contraction in the hyperalgesic muscle ipsilateral to the affected ureter at the lumbar level but not in the contralateral, non-hyperalgesic muscle, and the extent of these indices was proportional to the degree of visceral pain behavior and referred hyperalgesia recorded in the animals. In the same model, c-Fos activation was found in the spinal cord not only in sensory neurons but also in motoneurons, significantly more on the affected side (100,101).

Reflex arc activations have been indicated as contributing mechanisms also to the skin/ subcutis referred changes (102). In this case, the efferent branch of the reflex would be represented by sympathetic efferents toward the superficial somatic tissues. This hypothesis, based on the clinical observation of the reduction of referred superficial changes in patients after blocking of the sympathetic efferents toward the referred area, still needs to be confirmed experimentally in standardized conditions (103-105).

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