Assessment of intraoral mucosal pain induced by the application of capsaicin

Objective To develop an objective method for assessing nociceptive behaviour in an animal model of capsaicin-induced intraoral pain. Changes in nociceptive responses were also examined after injury to the inferior alveolar nerve (IAN). Design Nociceptive responses evoked by the intraoral application of various doses of capsaicin were analyzed in lightly anaesthetized rats. The number of c-Fos protein-like immunoreactive (Fos-LI) neurons in the medullary dorsal horn (MDH) induced by the intraoral application of capsaicin was measured. Behavioural and c-Fos responses were also examined 14 days after injury to the IAN. Results Larger doses of intraoral capsaicin (1, 10 and 100 μg) induced vigorous licking behaviour and c-Fos response in the MDH in a reproducible manner. The magnitudes of both behavioural activity and the c-Fos response from the 10 and 100 μg doses of capsaicin were significantly greater than that by the 1 μg dose. Injury to the IAN exaggerated the behavioural and c-Fos responses evoked by intraoral capsaicin. Conclusions The intraoral application of capsaicin is a valid and reliable method for studying intraoral pain and hyperalgesia following nerve injury

Effect of connective tissue growth factor (CCN2/CTGF) on proliferation and differentiation of mouse periodontal ligament-derived cells

Background: CCN2/CTGF is known to be involved in tooth germ development and periodontal tissue remodeling, as well as in mesenchymal tissue development and regeneration. In this present study, we investigated the roles of CCN2/CTGF in the proliferation and differentiation of periodontal ligament cells (murine periodontal ligament-derived cell line: MPL) in vitro. Results: In cell cultures of MPL, the mRNA expression of the CCN2/CTGF gene was stronger in sparse cultures than in confluent ones and was significantly enhanced by TGF-β. The addition of Recombinant CCN2/CTGF (rCCN2) to MPL cultures stimulated DNA synthesis and cell growth in a dose-dependent manner. Moreover, rCCN2 addition also enhanced the mRNA expression of alkaline phosphatase (ALPase), type I collagen, and periostin, the latter of which is considered to be a specific marker of the periosteum and periodontium; whereas it showed little effect on the mRNA expression of typical osteoblastic markers, e.g., osteopontin and osteocalcin. Finally, rCCN2/CTGF also stimulated ALPase activity and collagen synthesis. Conclusion: These results taken together suggest important roles of CCN2/CTGF in the development and regeneration of periodontal tissue including the periodontal ligament.</p

Basic research and clinical investigations of the neural basis of orofacial pain

Background: Trigeminal nerve injury or orofacial inflammation causes severe pain in the orofacial regions innervated by uninjured nerves or uninflamed tissues as well as injured or inflamed tissues. Pathological orofacial pain associated with trigeminal nerve injury or inflammation is difficult to diagnose and treat. Highlights: To develop appropriate treatments for patients with orofacial pathological pain, various animal models of trigeminal nerve injury or orofacial inflammation have been developed. Further, the possible mechanisms involving the trigeminal ganglion (TG), trigeminal spinal subnucleus caudalis (Vc), and upper cervical spinal cord (C1-C2) have been studied. Conclusions: 1) Neurotransmitters released from the somata of TG neurons are involved in peripheral sensitization. 2) Neurotransmitter release from TG neurons is decreased by botulinum toxin-type A administration, suggesting that this toxin suppressed neurotransmitter release and alleviated the neuropathic pain-related behavior. 3) Altered states of glial cells and nociceptive neurons, in the Vc and C1-C2 are involved in pathological orofacial pain associated with trigeminal nerve injury or orofacial inflammation. 4) The trigeminal sensory nuclear complex, especially the trigeminal spinal subnucleus oralis, is involved in normal and pathological orofacial pain conditions after peripheral nerve injury. 5) Neuroimaging analyses have suggested functional changes in the central and peripheral nervous systems in neuropathic pain conditions