Cat dental pulp after denervation and subsequent re-innervation: changes in blood-flow regulation and distribution of neuropeptide-, GAP-43- and low-affinity neurotrophin receptor-like immunoreactivity.
The effects of unilateral extramandibular inferior alveolar nerve injury on pulpal blood-flow responses to electrical stimulation and i.v. injections of substance P (SP) in cat mandibular canine teeth with a dentinal lesion were investigated with laser Doppler flowmetry. After blood-flow recordings, the teeth were fixed and the pulps were examined with light and electron microscopy. The distribution of pulpal SP, neurokinin A (NKA), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), growth-associated protein (GAP-43) and low-affinity neurotrophin receptor (LANR)-like immunoreactivity was examined with immunohistochemical fluorescence microscopy. Blood-flow recordings, performed at 10 days and 1 month postoperatively, showed that vasodilation, occurring in control teeth after bipolar electrical stimulation of the tooth crown, was absent in the denervated pulps, whereas at 3 months, five of six teeth had regained responsiveness, although at a low level. There was enhanced vasodilation (by 370%) to SP injections (400 fmol i.v.) at 10 days in denervated pulps. Such supersensitivity was reduced at 1 month despite the apparent lack of nerve fibers, and the response fell further towards the level in control teeth at 3 months when pulpal axons reappeared. At 10 days and 1 month postoperatively, light and electron microscopy demonstrated that surgery had resulted in total pulpal denervation. At 3 and 6 months, a large number of regenerated pulpal axons reappeared, in accordance with previous findings. At 10 days and 1 month after nerve transection immunohistochemistry showed a complete loss of pulpal immunoreactivity to all the neuropeptides that were studied. At 3 and 6 months, neuropeptide immunoreactivity reappeared but far fewer number of pulpal nerve fibers were SP-, NKA- and CGRP-immunoreactive than under normal conditions, as demonstrated by double-labeling experiments with GAP-43- or LANR-antiserum. The results indicate that pulpal hemoregulatory functions, which are lost after denervation, do not return to normal levels after nerve regeneration. This malfunction may be caused by inadequate target re-innervation and/or a deficiency of neuropeptides in the re-innervated pulp.
Olgart
L
L
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Edwall
L
L
Fried
K
K
D000818:Animals; D002415:Cats; D003714:Denervation; D003782:Dental Pulp / Q000098:blood supply / Q000294:innervation* / Q000378:metabolism; D004558:Electric Stimulation; D005260:Female; D019922:GAP-43 Protein; D006133:Growth Substances / Q000378:metabolism; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D008562:Membrane Glycoproteins / Q000378:metabolism; D008854:Microscopy, Electron; D009416:Nerve Regeneration; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D012039:Regional Blood Flow; D013373:Substance P / Q000494:pharmacology; D014018:Tissue Distribution
D019922:GAP-43 Protein; D006133:Growth Substances; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D017475:Receptors, Nerve Growth Factor; D013373:Substance P