Timo Hirvonen

The neurophysiological basis and the role of inflammatory reactions in dentine hypersensitivity.

Recent studies indicate that intradental A-type nerve fibres are responsible for the sensitivity of dentine and are activated by fluid movements in dentinal tubules (hydrodynamic mechanism). The patency of the tubules affects dentine sensitivity to a great extent. Both A delta- and A beta-type nerve fibres respond to dentinal (hydrodynamic) stimulation in a similar way. Only a few studies have been made on the regional sensitivity of dentine or the receptive areas of intradental nerve fibres. The results indicate that the fibres innervating different parts of coronal dentine are equally sensitive to dentinal stimulation but those in the cervical area may be less responsive. Inflammation in the pulp can considerably alter dentine sensitivity. In dog teeth with chronically exposed dentine, nerve responses to hydrodynamic stimulation were reduced although other functional changes indicated nerve sensitization. This may be due to spontaneously occurring changes in the exposed dentine that block the tubules. In acute experiments on cat and dog teeth with open dentinal tubules, certain inflammatory mediators increase the sensitivity of the responding nerve fibres. It seems that intradental C-fibres do not respond to hydrodynamic stimulation of dentine. They are polymodal and activated when external stimuli reach the pulp proper. They could perhaps mediate the dull pain connected with pulpitis. However, they might also have an important modifying effect on dentine sensitivity because they can release neuropeptides, which function in the inflammatory reactions.

Activation of heat-sensitive nerve fibres in the dental pulp of the cat.

Abstract We have recorded responses of inferior alveolar nerve fibres to heating of the intact enamel of the canine tooth crown in anaesthetized cats. After identification of intradental nerve units by monopolar electrical stimulation, the tooth was heated with an electrothermal stimulator (Peltier element). The rate of temperature change in the tooth was considerably slow (< l°C/sec). Responses of 37 heat‐sensitive units were recorded. They were all quite slowly conducting (CV = 1.7 ± 0.7 (S.D.) m/sec). Only 8 fibre units with conduction velocity below 3.5 m/sec did not respond to heating. The mean threshold temperature was 43.8 ± 3.4 (S.D.)°C. Nerve activity appeared as irregular bursts of action potentials. When heating was repeated at short intervals (2–3 min), an elevation in the thresholds was noticed. After cooling or a recovery period of about 10 min the thresholds for heating returned towards the initial ones, but they still remained somewhat elevated. This change in thresholds might have been due to heat induced injury in pulp tissue. When heating was stopped the activity ceased with declining temperature regardless of the temperature reached during the stimulation. Spontaneous firing never occurred. Not one of the units with a conduction velocity above 3.5 m/sec (n = 28,CV = 13.2 ± 7.1 (S.D.) m/sec) were activated by heating. Cooling of the tooth did not induce responses in any of the recorded units. Only 3 of 10 slowly conducting units fired, when pulp was mechanically irritated. On the other hand 11 of 14 fast conducting units were mechanosensitive. It is concluded that there exist differences in heat sensitivity of fast and slowly conducting pulp nerve units in the cat. The possible activation of slowly conducting intradental nerve fibres also in man might be significant in mediation of pain sensations induced by heating of the tooth crown.

Activation of intradental nerves in the dog to some stimuli applied to the dentine

Both scraping of superficial dentine and air blasts induced bursts of action potentials in 19 out of 22 units immediately. In 5 out of 16 units 4.9 mol/l CaCl2-solution was also effective. Dry absorbent cotton activated 5 out of 16 units with a 10-20 s latency. All 18 units tested responded to mechanical irritation of the pulp. Acid etching of dentine made the units more sensitive. Resin impregnation abolished the responses. Drilling of dentine with a turbine bur induced responses of the same type as air blasts. Three units responded to heat and 2 also to cold. Hypertonic NaCl-solution was only effective when applied either to the pulp (in 9 out of 12 units) or to the inner dentine (in 5 out of 17 units). It is concluded that intradental nerve fibres sensitive to several different stimuli exist in the dog. Many of the stimuli used induce fluid flow in dentinal tubules in vitro. Nerve activation might have been due to the same mechanism with all stimuli used, possibly to mechanical distortion of the peripheral pulp tissue as a result of the fluid flow. The findings support the hydrodynamic hypothesis of dentine sensitivity.

The excitability of dog pulp nerves in relation to the condition of dentine surface.

Sixteen intradental A-fiber units (cv 24.5±4.8 (SD)m/s) were identified with monopolar electrical stimulation of the dogs canine tooth. All of the units were activated by drilling and probing of dentine, 15 units by air blasts. Scanning electron microscopy of epoxy resin replicas and specimens of dentine showed that after acid etching of dentine, the apertures of dentinal tubules were open. Accordingly, nerve responses to probing and air blasts could be easily evoked. After drilling and resin or potassium oxalate impregnation, the apertures were partly or completely blocked and nerve responses were weak or totally absent. The results indicate that intradental A-fibers are responsible for dentine sensitivity. The responsiveness of these fibers can be affected by obstructing and opening the dentinal tubules.

A quantitative electron-microscopic analysis of the axons at the apex of the canine tooth pulp in the dog

The morphology of the dog intradental nerves has not been studied in detail, although dogs have been increasingly used in electrophysiological experiments on pulp nerve function. In this investigation electron microscopy and morphometric analysis were used to study the number and dimensions of the axons at the apex of the dog canine tooth. Two upper and two lower canines, each taken from a different animal, were used. The average number of axons entering a tooth was 2,089 (range: 1,241-3,034), 74.3% (range: 62.2-77.9%) of which were unmyelinated. The mean circumference of the myelinated and unmyelinated axons ranged from 11.1 to 13.9 microns and from 1.3 to 1.7 micron, respectively. Of the myelinated axons 13.7% had a circumference over 19 microns, which is considered to be the upper limit of the A delta-class. Of the unmyelinated axons 13.8% showed apposition to each other and 20% were partly exposed to the extracellular space; these features could, in part, offer the morphological basis for the extreme pain sensitivity of the tooth. The findings of the present study were considered in general to be comparable to the results of earlier histological and electrophysiological studies on pulp nerves of different species. Thus, it seems that the dog tooth is an adequate model for studying the pulp nerve function and morphology.

Conduction velocities of single pulp nerve fibre units in the cat : Acta physiol. scand., 116 (1982) 209–213

Evidence for the existence of peptide and nonpeptide morphine-like materials in mouse brain: effect of an analgesic intracerebroventricular dose of acetylcholine on their levels. T.T. Chau, C. Izazola-Conde and W.L. Dewey (Dept. of Pharmacology, Medical College of Virginia, Richmond, Va., U.S.A.), J. Pharmacol. Exp. Ther., 222 (1982) 612-616. It has been demonstrated that i.c.v. administered acetylcholine inhibited the writhing response induced by p-phenylquinone and prolonged tail-flick latency in mice. Such antinociceptive effects were inhibited by several narcotic antagonists in the same rank order of potency in which they antagonized the analgesic effects of morphine (Pedigo et al., 1975). The present work describes the results of studies which deal with the possible release of endogenous opioid substances from mouse brain after i.c.v. administration of acetylcholine in an attempt to explain the mechanism of the antinociceptive action of this compound. Brains of mice pretreated with saline or 40 pg of acetylcholine (ACh) i.c.v. were fractionated according to published procedures. The fractions yielded 4 peaks of inhibitory activity in the radioreceptor assay. Intraventricular ACh decreased the inhibitory activity of peak I (fractions lo-19), increased that of peak II (fractions 20-24) and peak III (fractions 25-29) and did not change the activity of peak IV in the radiotracer binding assay. Peaks I, III and IV were potent inhibitors of the coaxially stimulated guinea-pig ileum and such inhibitory activity was not destroyed by incubation with trypsin, carboxypeptidase or by naloxone. Intraventricular ACh did not alter the activity of the 3 peaks on coaxially stimulated ileum bioassay. Peaks II and III both caused a contraction of the non-stimulated guinea-pig ileum and their effect was reduced either by enzymatic treatment (peak II) or by atropine (peak III). No difference was observed between the effects of each peak in saline or ACh-treated mice in this test. All 4 peaks were active in the writhing test. The results suggest the presence of several opiate-like materials in the brain. The endogenous opioids appear to be a mixture of endorphin-like peptides as well as non-peptides. The data also indicate the presence of spasmogenic peptides with some opiate properties.