Matti Närhi

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.

The effect of temporal parameters on subjective sensations evoked by electrical tooth stimulation

&NA; The effect of stimulus duration and frequency on subjective sensations evoked by electrical tooth stimulation was studied in 12 subjects. The sensory responses were classified using 5 equi‐sensation categories (perception threshold, prepain, pain threshold, moderate pain, intense pain). Both continuously increasing and randomised stimuli were applied. A comparison was made with the activation thresholds of intradental A‐ and C‐fibres in the cat. The mean threshold of intradental A‐fibres was lower than the perception threshold at all pulse durations. Perception threshold decreased with increasing stimulus frequency. Current intensities which evoked prepain at a stimulus frequency of 1 Hz were rated as pain at 20 Hz. At supraliminal pain levels the effects of summation were more marked. High‐frequency stimulation produced intense pain sensations at intensities well below the activation thresholds of pulpal C‐fibres in the cat. We conclude that both perception and pain thresholds and supraliminal pain are modified by temporal summation, and that activation of different pulpal fibre populations is not responsible for production of prepain and pain sensations.

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.

The effect of fentanyl on c-fos expression in the trigeminal brainstem complex produced by pulpal heat stimulation in the ferret

We have previously shown that Fos-like immunoreactivity (Fos-LI) is evoked in the brainstem of ferrets following stimulation of pulpal A delta and C fibers originating from the maxillary canine. This study evaluated the effects of the mu-opioid receptor agonist fentanyl on Fos expression evoked by noxious thermal stimulation of the right maxillary and mandibular canines in pentobarbital/chloral hydrate anesthetized adult male ferrets. Pulpal heating evoked Fos expression in two distinct regions of the spinal trigeminal nuclear complex: the transitional region between subnucleus interpolaris and caudalis (Vi/Vc) and within the subnucleus caudalis (Vc). More Fos positive cells were expressed in both regions ipsilateral to the site of stimulation compared with the contralateral side (P < 0.05, ANOVA). Pretreatment with fentanyl significantly and dose-dependently suppressed the number of Fos positive cells in both the Vi/Vc transitional region and Vc (P < 0.05, ANOVA). The suppressive effect of fentanyl on Fos expression was blocked by the intravenous administration of naloxone, an opioid antagonist, indicating a specific opioid receptor effect. In addition, opioid receptor antagonism with naloxone alone enhanced Fos expression in Vi/Vc and Vc in response to heat stimulation. The administration of naloxone without heat stimulation failed to evoke Fos expression in Vi/ Vc and Vc. These findings suggest that the activation of trigeminal Vi/Vc and Vc neurons by noxious dental heat stimulation is controlled by a naloxone sensitive endogenous opioid system as indicated by Fos expression. Collectively, these results suggest that neuronal populations in Vi/Vc and Vc regions may contribute to pain responses to noxious dental stimulation and these responses can be modulated by both endogenous and exogenous opioids.

Trigeminal c-Fos expression and behavioral responses to pulpal inflammation in ferrets.

&NA; Injury to peripheral dental tissues evokes dynamic alternations in central sensory pathways. We have previously reported that transient stimulation of the dental pulp with noxious heat evokes the induction of the immediate early gene product Fos in the transitional region between subnucleus interpolaris and caudalis (Vi/Vc) and subnucleus caudalis (Vc). A question arises as to whether similar changes occur in response to inflammation to the tooth pulp. In this study, the effects of pulpal inflammation produced by bacterial lipopolysaccharide (LPS) on face‐grooming behavior and trigeminal Fos expression were examined. Face‐grooming behaviors were recorded daily for 3 days pre‐ and 24, 48 and 72 h post‐ LPS or saline application. All animals were perfused 72 h post‐ LPS or saline application. Brainstems were processed for Fos‐like immunoreactivity (Fos‐LI). Teeth were processed for H&E staining. Histological examination of LPS‐treated teeth revealed features of an acute pulpitis. Moreover, LPS‐treated animals showed greater face‐grooming activity (i.e. tongue protrusions) directed to the injured tooth than the sham‐operated group. The number of Fos‐positive neurons was greater in the trigeminal subnucleus caudalis (Vc) and the transitional regions (Vi/Vc) in LPS‐treated animals compared with sham‐operated animals, and greater in the deeper laminae than the superficial laminae of each trigeminal region. LPS treatment did not evoke Fos expression in the rostral trigeminal regions above Vi/Vc. These results demonstrate that LPS‐induced pulpal inflammation results in significant alterations in the Vi/Vc and Vc, and such changes may underlie the observed nociceptive behavioral responses and may play an important role in producing a symptomatic pulpitis in humans.

Spatial integration of cold pressor pain sensation in humans.

Spatial integration of cold pressor pain (CPP) in the hand was studied in healthy human subjects by measuring the latency to the ice water-induced first pain sensation with and without conditioning CPP. CPP alone showed a marked spatial summation effect. When conditioning and test CPP were applied at the same time, conditioning CPP suppressed test CPP both in an adjacent and a distant site. When test CPP was applied after the conditioning CPP (i.e. pain induced by conditioning CPP was considerably stronger than that evoked by test CPP) conditioning CPP suppressed the test CPP only in a distant site but enhanced it in an adjacent site. A decrease in the test stimulus area increased the suppressive effect by conditioning CPP. Thus, CPP shows spatial summation or inhibition depending on experimental parameters.

Biotransformational and neurophysiological changes in rabbits exposed to lead.

Lead was administered to adult male rabbits in drinking water at a 0.1% concentration for four and five week periods. The lead contents were determined in the central and peripheral nervous tissues and in the liver, kidney, and intestinal mucosa. The conduction velocity of sciatic nerve and the activities of drug metabolizing enzymes in other tissues were determined. The lead concentration in the blood was at a steady state at four to five weeks of exposure. Lead accumulated in all tissues except the brain. The brain lead concentration was 40 to 50% of that in the blood, indicating the existence of a blood-brain barrier. However, the lead concentration in the sciatic nerve increased significantly from four to five weeks of exposure and exceeded that in the blood. This indicates the lack of a blood-nervous tissue barrier in the sciatic nerve allowing a continuous accumulation of lead. This accumulation affected the function of the sciatic nerve; motor nerve conduction velocity decreased from the control level (58.3±7.4 m/sec) to 43.8±6.3 m/sec after the four-week exposure and to 35.0 ± 1.3 m/sec at 5 weeks of exposure. After five weeks of exposure, no changes in the hepatic, intestinal, or renal drug metabolizing enzyme activites were found. These results suggest that motor nerve conduction velocity is affected by lead exposure prior to any influence on biotransformation enzymes.

Tissue concentrations and interaction of zinc with lead toxicity in rabbits

Adult male rabbits were exposed to lead (0.2%), zinc (0.5%) or to both lead and zinc (0.2% and 0.5%) which were given in the drinking water as acetates for 2 weeks or 4 weeks. Blood lead levels in lead exposed rabbits were about 15-fold in comparison with the controls after 2 weeks exposure and remained at this level after further exposure, but when zinc was given with lead the blood lead level doubled from 2 weeks to 4 weeks. In rabbits having both lead and zinc, the cerebral lead concentration was much lower than in rabbits exposed only to the respective amount of lead. No such effect was found in the cerebellum or sciatic nerve. Zinc did not prevent lead accumulation in the parenchymal tissues. Only a rather low induction of drug metabolizing enzyme activities was found in the liver of lead-exposed rabbits and zinc did not modify this induction. The results suggest that, although zinc might delay the lead accumulation in the cerebrum, it has little value in preventing peripheral neuropathy or metabolic alterations caused by lead.