Sensory deficit in Parkinson's disease: evidence of a cutaneous denervation

Abstract

Sensory disturbances are part of the clinical picture of Parkinson's disease. Abnormalities in sensory processing, through a basal ganglia involvement, are thought to be responsible for the sensory dysfunction since sensory nerve conduction velocity (NCV) is usually normal. However, NCV does not examine small fibres or terminal endings of large sensory fibres, whereas skin biopsy is more suitable for these purposes. To evaluate peripheral sensory nerves in Parkinson's disease, we studied cutaneous free and encapsulated sensory nerve endings in 18 patients and 30 healthy controls using 3-mm punch biopsies from glabrous and hairy skin. Ten patients had additional skin biopsies from the contralateral side. Further evaluation included NCV and Quantitative Sensory Testing. Parkinson's disease patients showed a significant increase in tactile and thermal thresholds (P < 0.01), a significant reduction in mechanical pain perception (P < 0.01) and significant loss of epidermal nerve fibres (ENFs) and Meissner corpuscles (MCs) (P < 0.01). In patients with bilateral biopsies, loss of pain perception and ENFs was higher on the more affected side (P < 0.01). We found evidence suggesting attempts at counteracting degenerative processes as increased branching, sprouting of nerves and enlargement of the vascular bed. Morphological and functional findings did not correlate with age or disease duration. Disease severity correlated with loss of MCs and reduction in cold perception and pain perception. We demonstrated a peripheral deafferentation in Parkinson's disease that could play a major role in the pathogenesis of the sensory dysfunction.

A new device to quantify tactile sensation in neuropathy

“…4 More recently, reduced MC density, distorted MC structure, focal thinning or loss of myelin, and short myelin internodes coupled with decreased sensitivity to touch have been reported. [5][6][7] Functional studies of touch conveyed by cutaneous mechanoreceptors in glabrous skin found that detection of small raised dots (bumps) on a smooth surface using the finger pad was signaled by MCs. 8,9 Based on these studies, we devised a simple device called the Bumps to quantify tactile sensitivity on the finger pads.…”

Pain perception in Parkinson’s disease: A systematic review and meta-analysis of experimental studies

“…When a study provided insufficient data for inclusion, corresponding authors were contacted up to 3 times over an 8-week period to request additional data. Of 8 author groups contacted, 6 [3,25,28,41,43,54] provided data sufficient to permit study inclusion.…”

“…One study [43] reported implausible pain thresholds (9.1-12.4˚C) for heat stimulation (values for other stimuli were plausible), and a further study [48] reported means and SDs for pain threshold highly inconsistent with reported p-values (even when SDs were treated as SEMs), and so this specific data were excluded. Three studies reported pain tolerance data, and 3 other studies reported 'threshold to moderate pain' (where participants were told to withdraw from noxious stimulation when experiencing moderate pain).…”

“…Although it is difficult to identify such mechanisms from the current available data, these could include a loss of epidermal nerve fibres [43] or deficiencies in other, non-dopaminergic pain pathways. An alternative explanation is that pain hypersensitivity is entirely mediated by dopamine deficiency in PD but that study medication dosages were insufficient to restore dopamine neurotransmission to normal physiological levels.…”

“…While pain in PD is often precipitated by muscular rigidity and/or postural abnormalities [22], neurodegenerative processes could potentially affect not only motor function, but also peripheral [43] and brain [19] pathways involved in pain processing. For example, degradation of dopamine-producing cells in the substantia nigra may impair natural analgesia by disrupting the dopamine-mediated descending pathways that block transmission of ascending nociceptive signals from the spinal cord [19].…”