Sensory neuropeptide mRNA up‐regulation is bilateral in periodontitis in the rat: a possible neurogenic component to symmetrical periodontal disease

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Abstract
Periodontal disease is a common multifactorial chronic inflammatory disease in humans. In inflammatory conditions that are known to be associated with changes in nociception, such as arthritis, the neuronal expression of the proinflammatory neuropeptides, substance P and calcitonin gene‐related peptide is altered. In this study the expression of these neuropeptides' mRNAs has been studied in an inflammatory model that shows no behavioural evidence of altered nociception. Periodontitis was induced in male rats by intragingival injection of lipopolysaccharide adjacent to the second right mandibular molar. The animals were killed at various times after lipopolysaccharide injection and right and left trigeminal ganglia and brain were processed for in situ hybridization for β‐preprotachykinin and α‐calcitonin gene‐related peptide mRNAs. Expression of both neuropeptide mRNAs was significantly increased only in small neurons in the mandibular division of the trigeminal ganglion ipsilateral to the LPS injection from 3 to 10 days postinjection. Neuropeptide mRNA expression was also significantly increased in the contralateral trigeminal ganglion at day 10. No significant changes in neuropeptide mRNA levels were seen in the maxillary and ophthalmic divisions of the trigeminal ganglia or in the trigeminal mesencephalic nucleus. The up‐regulation of substance P and CGRP mRNAs in periodontal disease suggests that this is associated with the inflammatory process rather than nociception, as this disease does not appear to result in altered nociception in either rats or humans. The contralateral alteration in neuropeptide mRNA expression suggests a role for neurogenic mechanisms in the development of periodontal disease.