| Abstract No.: | C-C3106 |
| Country: | Canada |
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| Title: | CHANGES IN SENSORY AND AUTONOMIC FIBER INNERVATION IN THE RAT LOWER LIP SKIN FOLLOWING A SENSORY NERVE LESION |
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| Authors/Affiliations: | 1 Anna Taylor*; 1 Geraldine Longo; 1 Alfredo Ribeiro-da-Silva;
1 McGill University, Montreal, QC, Canada
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| Content: | Objectives: The skin is innervated by two populations of small diameter sensory fibres, the peptidergic and non-peptidergic, which transmit nociceptive information to the central nervous system. Peripheral nerve injuries leading to a neuropathic pain state have been shown to lead to changes in peptidergic and autonomic fiber innervation, however, the non-peptidergic innervation pattern in the skin for normal and neuropathic tissue is less known. In the present study, we used immunofluorescence and confocal microscopy to investigate the pattern of non-peptidergic and parasympathetic innervation in uninjured and injured cutaneous tissue from the rat lower lip skin.
Materials and Methods: A neuropathic pain state was induced in male Sprague-Dawley rats by a bilateral chronic constriction injury (CCI) of the mental nerve, a purely sensory branch of the trigeminal nerve. Injured and sham operated animals from several time points were tested for mechanical allodynia using von Frey filaments directed towards the lower lip. The animals were then anaesthetized and perfused with histological fixatives, and the lower lip was extracted and processed for immunofluorescence using antibodies directed towards the purinergic receptor P2X3 and the vesicular acetylcholine transporter (VAChT) to specifically label non-peptidergic nociceptors and parasympathetic fibres, respectively.
Results: The innervation of the uninjured upper dermis by P2X3 immunoreactive (IR) fibres was extensive, and many fibres crossed the dermal-epidermal junction and formed a dense network throughout the entire epidermis. This fibre population formed the predominant fibre population within the epidermis. Two weeks following nerve injury, there was a significant loss of P2X3-IR fibres in the epidermis and upper dermis. By four weeks, however, the density of innervation of these fibres had returned to normal levels in the upper dermis. In contrast, behavioural analysis of these animals showed that there was significant mechanical allodynia when compared to sham animals beginning at 2 weeks following lesion. This increased sensitivity persisted to all time points measured (up to 6 months). Interestingly, both sympathetic and parasympathetic fibres displayed a robust migration into the upper dermis, an area in which they are normally absent, 2 weeks following nerve lesion. These ectopic autonomic fibres persisted to all time points tested. This pattern of innervation more closely correlates with the neuropathic behavioural profile of the animals, and suggest they play an important role in the aberrant pain processing following nerve injury.
Conclusions: These results suggests that P2X3-IR fibres may play a primary role in the detection of noxious stimuli in uninjured cutaneous tissue, and changes in non-peptidergic innervation and autonomic fibres may play an important role in the development and maintenance of neuropathic pain states.
Research funded by CIHR. |
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