The influence of chemical sympathectomy on pain responsivity and alpha 2-adrenergic antinociception in neuropathic animals.

We studied the effect of chemical sympathectomy by 6-hydroxydopamine (6-OHDA) on pain behavior and alpha(2)-adrenergic antinociception in rats with a spinal nerve ligation-induced neuropathy. For assessment of alpha(2)-adrenergic antinociception, the rats were treated systemically with two alpha(2)-adrenoceptor agonists, one of which only poorly (MPV-2426) and the other very well (dexmedetomidine) penetrates the blood-brain barrier. Moreover, the effect of MPV-2426 on spontaneous activity of dorsal root nerve fibers proximal to the nerve injury was determined. Systemic treatment with 6-OHDA produced a marked decrease in immunocytochemical labeling of sympathetic nerve fibers in the skin but it produced no marked change in basal pain sensitivity to mechanical stimulation either in neuropathic or sham-operated animals. Systemic administration of MPV-2426 and dexmedetomidine produced a dose-dependent tactile antiallodynic effect in neuropathic animals. Intraplantar injection of MPV-2426 had an identical antiallodynic effect independent of whether it was injected into the neuropathic or contralateral hindpaw. In a test of mechanical nociception and hyperalgesia, dexmedetomidine markedly attenuated pain responses in all experimental groups, whereas MPV-2426 had a weak but significant pain attenuating effect only in neuropathic animals. In the tail flick test, both alpha(2)-adrenoceptor agonists had a significant antinociceptive effect. The pain attenuating effect of MPV-2426 was enhanced by pretreatment with 6-OHDA, except in a test of tactile allodynia. MPV-2426-induced modulation of spontaneous activity was not a general property of dorsal root fibers proximal to the injury. The results indicate that a chemical destruction of sympathetic postganglionic nerve fibers innervating the skin does not markedly influence cutaneous pain sensitivity nor is it critical for the alpha(2)-adrenoceptor agonist-induced attenuation of pain behavior in neuropathic or non-neuropathic animals. Chemical sympathectomy, independent of neuropathy, enhanced the pain attenuating effect by MPV-2426, probably due to a peripheral action, whereas in non-sympathectomized control and neuropathic animals peripheral mechanisms have only a minor, if any, role in the alpha(2)-adrenoceptor agonist-induced antinociception.

Allodynia induced by regenerating axons is not positively correlated with degree of autotomy in the rat.

We studied in the rat whether the incidence of autotomy correlated positively with severity of tactile allodynia induced by regenerating axons. Before transection and surgical repair of the sciatic nerve, the status of sensory function was studied by stimulating mechanically the central part of the plantar paw with von Frey-hairs. Thereby we determined the threshold to evoke the hindpaw withdrawal reflex. One and 2 months after the nerve transection and repair, the thresholds of the traumatized paws were lower than the pre-trauma thresholds. The contralateral paw withdrawal thresholds did not change during the follow-up time. The results indicated that regenerating axons may cause tactile allodynia and that the severity of this allodynia does not correlate positively with the incidence of autotomy. We found no contralateral allodynia after nerve transection and repair.

The effect of a selective alpha2-adrenoceptor antagonist on pain behavior of the rat varies, depending on experimental parameters.

Effects of atipamezole, an alpha2-adrenoceptor antagonist, in various acute pain tests were studied in the rat. Atipamezole (at doses > or = 0.1 mg/kg I.P.) and idazoxan, another alpha2-adrenoceptor antagonist (2.5 mg/kg, I.P.), increased licking latency in the hot-plate test. Bilateral administration of atipamezole (10 microg) into the locus coeruleus did not increase licking latency in the hot-plate test. Medetomidine (an alpha2-adrenoceptor agonist; 1-3 mg/kg) or repeated pre-exposures to the testing apparatus reversed the effect of atipamezole (1.5 mg/kg) in the hot-plate test. Atipamezole also increased the latency to mechanically induced licking/biting response at a dose of 1.5 mg/kg, but not at lower doses. In the heat-induced tail-flick test, in contrast, atipamezole at doses of 0.1 and 1.5 mg/kg produced a medetomidine-reversible decrease of response latencies. This facilitation of the tail-flick response disappeared if the intensity of the heat stimulus was high. At a dose range from 0.03 to 1.5 mg/kg atipamezole did not significantly alter the paw withdrawal latency to noxious mechanical stimulation, nor pain behavior in the formalin test. Responses to nociceptive spinal dorsal horn neurons were not modulated by atipamezole (1 mg/kg) in anesthetized spinalized rats. The results indicate that an alpha2-adrenoceptor antagonist may have variable effects in behavioral pain tests, depending on habituation of the experimental animals to the testing conditions, the dose of the drug, the type of behavioral response and the submodality or the intensity of the noxious test stimulus. The atipamezole-induced changes in pain behavior observed in this study may rather be explained due to action on motor expression of pain than due to modulation of nociception.

Use of paper for treatment of a peripheral nerve trauma in the rat.

Reinnervation of the muscles and skin in the rat hindpaw was studied after transection and attempted repair of the sciatic nerve. Reconnecting the transected nerve with lens cleaning paper was at least as effective in rejoining the transected nerves as traditional microsurgical neurorraphy. Paper induced a slightly bigger fibrous scar around the site of transection than neurorraphy, but this scar did not cause impairment of functional recovery or excessive signs of neuropathic pain. We conclude that a paper graft can be used in restorative surgery of severed peripheral nerves.

Evidence for slowly conducting afferent fibres innervating both tooth pulp and periodontal ligament in the cat.

The presence of afferent nerve fibres branching to innervate both the dental pulp and periodontal ligament was studied in pentobarbitone-anaesthetised cats. Extracellular single nerve-fibre recordings were made from fine filaments split from the proximally cut end of the inferior alveolar nerve. Nerve fibres were identified by bipolar constant-current stimulus pulses applied to the periodontal space via platinum wire electrodes. In each case activation of the nerve fibres was also attempted by monopolar electrical stimulation of the dental pulp via a platinum wire electrode inserted into the dentine. Eleven of 142 C fibres and 4 of 97 A delta fibres identified by electrical stimulation of the periodontal ligament also could be activated by electrical stimulation of the dental pulp. Fourteen of the 142 C fibres identified by electrical stimulation of the periodontal ligament exhibited discrete latency jumps at different suprathreshold stimulus strengths. Eight of them also could be activated by electrical stimulation of the dental pulp. Eight of the 15 fine branching afferent fibres were tested with non-electrical stimuli of both periodontal ligament and dental pulp by application of heat, cold and potassium chloride. Three of the 4 C fibres could be activated with at least one of these stimuli applied to both tissues. In one case receptive fields were located in both periodontal ligament and dental pulp. The remaining 5 slowly conducting fibres were activated only from one type of tissue. The results suggest that a small percentage (6%) of the slowly conducting nerve fibres in the inferior alveolar nerve innervate both the periodontal ligament and the dental pulp. According to their response behaviour they might be involved in nociception.

Can the alpha 2-adrenoceptor agonist-mediated suppression of nocifensive reflex responses be due to action on motoneurons or peripheral nociceptors?

To exclude the possibility that the suppression of nocifensive reflex responses induced by alpha 2-adrenergic agents is due to action on alpha-motoneurons or peripheral nociceptors, we studied the effect of medetomidine, an alpha 2-adrenoceptor agonist, on the monosynaptic reflex and on the primary afferent nociceptor-mediated antidromic vasodilator response in rats. Additionally, the effect on the dorsal root potential, an index of a transient excitability change in the central terminals of primary afferent fibers, was determined. Medetomidine was applied systemically at doses (100 and 300 micrograms/kg) which have proven strongly antinociceptive in previous studies. The amplitudes of a submaximal monosynaptic reflex volley or a submaximal dorsal root potential were not changed by medetomidine. Medetomidine induced a decrease of cutaneous blood flow but did not abolish the vasodilatatory response to antidromic stimulation of the sciatic nerve at C-fiber intensity as determined by the laser Doppler flow method. The results indicate that the alpha 2-adrenoceptor-mediated suppression of nocifensive reflex responses is not caused by a decreased excitability of motoneurons or peripheral nociceptors. An alpha 2-adrenoceptor agonist does not modulate the transient stimulus-evoked change in the excitability of central terminals of primary afferent fibers.

Activation of alpha 2-adrenergic receptors decreases nerve trauma-induced afferent barrage but not autotomy.

Effects of the selective alpha 2-adrenoceptor agonist, medetomidine, on a compound volley of a tibial nerve stimulation-evoked spinal reflex, pain-induced phrenic motor responses and on postoperative neuropathic pain behavior were studied in rats. Medetomidine (0.3 mg/kg) decreased the amplitude of the compound volley recorded from peroneal nerve in response to tibial stimulation in pentobarbital (40 mg/kg) anesthetized rats. Atipamezole, an alpha 2-adrenoceptor antagonist (1.5 mg/kg) fully restored the response when given 60 min after the medetomidine administration. Pain-evoked phrenic motor responses were completely inhibited upon combination anesthesia by pentobarbital (40 mg/kg) and medetomidine (0.3 mg/kg) (PB+M) but not upon plain pentobarbital anesthesia (50 or 60 mg/kg) (PB50,PB60). To study the effect of medetomidine on postoperative neuropathic pain behavior (autotomy), transection of sciatic nerve was done under PB+M, PB50 or PB60 anesthesia. No differences between the groups were found in the postoperative pain behavior during eight-week follow up. The results show that activation of alpha 2-adrenergic receptors by medetomidine under pentobarbital anesthesia mitigates trauma-induced afferent barrage, whereas it does not reduce the subsequent autotomy.

Blood flow increase in the orofacial area of humans induced by painful stimulation.

The purpose of this study was to investigate if painful stimulation produces blood flow changes in the tooth pulp and the facial skin in humans. Also, we attempted to find out if the possible blood flow changes induced by painful stimulation could be explained by central sympathetic and parasympathetic reflex mechanisms, by an antidromic activation of nociceptive axons (axon reflex), or by a change in central cardiovascular parameters. Laser Doppler flowmeter was used to assess the blood flow changes. Electrical tooth pulp stimulation at painful intensities induced a blood flow increase in the ipsilateral lip adjacent to the stimulus site, and vice versa. Nonpainful stimulation had no effects. Painful thermal stimulation of the upper lip also produced an increase in the blood flow of the ipsilateral upper incisor. The blood flow changes in the lip produced by dental stimulation were not correlated with changes in systemic blood pressure or heart rate. Painful electrical stimulation of the hand did not induce any changes in the pulpal blood flow, whereas painful dental stimulation produced a blood flow decrease in the finger but no change in the contralateral lip or cheek. In monkey experiments a regional block of the central conduction of the inferior alveolar nerve at the level of the mandibular foramen produced varying results: the blood flow increase in the lower incisor produced by noxious thermal stimulation of the ipsilateral lower lip was not abolished in two experiments but was abolished in other two experiments. It is concluded that painful stimulation can induce significant increases in the blood flow of the orofacial regions in humans. This increase is predominantly restricted to the region adjacent to the stimulus site and cannot be explained by changes in the central cardiovascular parameters. Central neuronal reflex mechanisms and an axon reflex may both underlie these blood flow increases.

A laminin graft replaces neurorrhaphy in the restorative surgery of the rat sciatic nerve.

We investigated the role of laminin in functional recovery of a peripheral nerve injury using electrophysiological and behavioral approaches on the rat sciatic nerve in vivo. These studies were complemented by neurofilament protein immunocytochemistry on the sciatic nerve 20 days after an operation, in which an 8-mm piece of the nerve was removed and replaced by a graft of laminin, its neurite outgrowth-promoting peptide, a control peptide, collagen, or by resuturing of the removed piece of the nerve. Electrophysiological measurements of muscle strength 4 months after the sciatic nerve transection showed that a laminin graft was as effective as neurorrhaphy in supporting functional recovery of an injured peripheral nerve. A laminin graft also significantly reduced autotomy in the operated animals. Immunocytochemistry confirmed that both a laminin graft and resuturing supported growth of the 200-kDa neurofilament-positive axons into the distal stump of the nerve within 20 days of operation. A graft with a neurite outgrowth-promoting peptide of the B2 chain of laminin supported similar axon growth, whereas another peptide graft also derived from laminin or a collagen graft did not support axon growth. All grafts allowed Schwann cell growth into the distal stumps of the nerves, but neurites accompanied them only in the regeneration-supporting grafts and in the resutured nerves. The Schwann cells of the regenerating nerves expressed high levels of the neurite outgrowth-promoting domain of the B2 chain of laminin, whereas the Schwann cells of the degenerating nerves failed to express this domain in the distal stumps of the degenerating nerves. These results provide the first in vivo evidence for the functional role of laminin in peripheral nerve regeneration. As the neurite outgrowth-promoting domain of the B2 chain of laminin is as efficient as laminin or resuturing in supporting a short-term recovery of an injured sciatic nerve, this area may be a regeneration-promoting domain of this glycoprotein. More importantly, as grafting significantly reduces post-traumatic pain behavior in the operated animals, the laminin graft surgery may provide a useful method for clinical restoration of the injured peripheral nerves.

Identification and characterization of afferent periodontal A delta fibres in the cat.

1. The presence and responsiveness of afferent periodontal A delta fibres was studied in pentobarbitone-anaesthetized adult cats. 2. Extracellular single fibre recordings were made from fine nerve filaments split from the proximally cut end of the inferior alveolar nerve. Periodontal nerve fibres were identified by constant current stimulus pulses applied via platinum wire electrodes inserted into the periodontal space of the lower canine tooth. 3. Of a total of 252 periodontal nerve fibres, 97 (37%) were classified as A delta fibres according to their conduction velocities (CV) (> 2.5 m s-1, < 30 m s-1) as determined by electrical stimulation of the periodontal ligament. The mean (+/- S.D.) conduction velocity was 11.0 +/- 7.7 m s-1 (n = 97; range: 2.6-28.2 m s-1). 4. A good exponential correlation (r = 0.85) was found between the electrical thresholds of the A delta fibres and their conduction velocities. 5. For four A delta fibres a complete stimulus-duration curve was determined. It followed rather well the I = I0/(1-et/tau) law, where I represents the stimulus amplitude, t the stimulus duration, I0 the rheobasic current and tau the time constant. 6. In the intact tooth none of the identified periodontal A delta fibres showed any ongoing activity in the absence of intentional stimulation. 7. The responses of sixteen electrically identified periodontal A delta fibres were tested by mechanical, thermal and chemical stimuli applied to the periodontal space. Seven of nine periodontal A delta fibres tested responded to mechanical forces applied to the tooth from different directions of which none could be activated by slight touch. A rudimentary directional sensitivity was seen. When a human tooth was stimulated by a mechanical stimulus of similar strength the sensation evoked was described as a dull, poorly localized pain. 8. Six periodontal A delta fibres were activated by heat and/or cold and/or chemical stimulation. Two of eight periodontal A delta fibres tested responded to heat and four of six A delta fibres tested responded to cold stimuli applied to the alveolar bone overlying the periodontal ligament; none of them responded to both types of thermal stimuli. Two of seven periodontal A delta fibres tested were activated by a saturated solution of potassium chloride applied locally to the periodontal ligament; two of these responded also to cold. 9. The response behaviour of periodontal afferent A delta fibres observed in this study suggests that they may play a role in periodontal nociception.

Effects of atipamezole, an alpha 2-adrenoceptor antagonist, on the anesthesia induced by barbiturates and medetomidine.

We studied the effects of atipamezole, an alpha 2-adrenoceptor antagonist, on hypnosis induced by medetomidine, an alpha 2-adrenoceptor agonist (1 mg/kg IP), and pentobarbital (40 mg/kg IP) by testing the righting reflex in the rat. The duration of antinociception was assessed with repeated pinch tests. Medetomidine-induced hypnosis and antinociception were inhibited by atipamezole at doses greater than 0.1 mg/kg. Atipamezole restored the righting reflex at a dose ratio that was 1:10 or more to that of medetomidine used to induce hypnosis. Subcutaneous atipamezole (1.5 mg/kg) increased the duration of hypnosis induced by pentobarbital (40 mg/kg) and pentobarbital + medetomidine (0.3 mg/kg). Hypnosis induced by methohexital (60 mg/kg IP) was also prolonged by atipamezole. The capacity of atipamezole to reverse the effects of medetomidine is also reduced in the presence of barbiturates. Thus, atipamezole should be used only at low doses to reverse a combination anesthesia induced by barbiturates and medetomidine.

Identification and characterization of afferent periodontal C fibres in the cat.

The presence of afferent periodontal C fibres was studied in pentobarbitone-anaesthetized cats. Extracellular single-fibre recordings were made from fine nerve filaments split from the proximally cut end of the inferior alveolar nerve. Periodontal nerve fibres were identified by constant-current stimulus pulses applied via platinum wire electrodes inserted into the periodontal space. Of 260 periodontal nerve fibres, 142 (55%) were classified as C fibres according to their conduction velocities (less than or equal to 2.5 m/sec) as determined by electrical stimulation of the periodontal ligament (c.v.p). The mean (+/- S.D.) c.v.p was 1.2 +/- 0.6 m/sec (n = 142; range: 0.3-2.5 m/sec). In addition, the axonal conduction velocity of 14 periodontal C fibres was determined by bipolar electrical stimulation of the trunk of the inferior alveolar nerve (c.v.n). On average the c.v.n was 42% higher than the c.v.p; the mean value was 1.7 +/- 0.8 m/sec (n = 14; range: 0.6-3.9 m/sec). Nevertheless, the classification of nerve fibres based on c.v.p proved to be reliable; only 1 fibre had a c.v.p less than 2.5 m/sec and a c.v.n greater than 2.5 m/sec and a c.v.n greater than 2.5 m/sec and was therefore reclassified as an A delta fibre. The responses of 30 electrically identified periodontal C fibres were tested by mechanical, thermal and chemical stimuli applied to the periodontal space. Thirteen of 19 periodontal C fibres tested responded to a strong mechanical force applied to the tooth from different directions while none could be activated by slight touch. A rudimentary directional sensitivity was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Response characteristics of tooth pulp-driven postsynaptic neurons in the spinal trigeminal subnucleus oralis of the cat.

Neuronal activity in the spinal trigeminal subnucleus oralis in response to electrical tooth stimulation was recorded in the anaesthetized cat in order to compare the electrophysiological characteristics of the oralis neurons with those of subnucleus caudalis and interpolaris neurons recorded in previous studies. The most sensitive oralis neurons had lower thresholds and shorter latencies than the most sensitive caudalis and interpolaris neurons. The thresholds of the oralis neurons were lower and their strength-duration curves flatter than those depicting liminal dental pain in man but similar to those depicting liminal jaw reflexes in the cat. Noxious conditioning stimulus elevated the threshold of only 1 of 10 neurons tested. The converging input from the skin and oral mucosa was from low-threshold mechanoreceptors. The results indicate that the response properties of the subnucleus oralis neurons differ significantly from those of other spinal subnuclei. Human pain thresholds cannot be explained by the liminal response properties of oralis neurons. These neurons might be important in the mediation of liminal reflex events evoked by dental stimuli.

Role of intradental A- and C-type nerve fibres in dental pain mechanisms.

The arousal of the two components of pain (the first rapid or sharp pain and the second dull pain) are considered to be related to activation of A delta- and C-type nociceptive primary afferents, respectively. The same dichotomy of pain sensations may also exist in teeth, although due to the short distance between the site of stimulation and the brain the two sensations might not be as clearly separated as in stimulation of, for example, the extremities. The sensations evoked by stimulation of human teeth vary according to the type of the stimuli applied. Low-intensity electrical stimulation is able to induce non-painful (prepain) sensations. At high current intensities pain is evoked. Drilling, probing and air-drying of exposed dentin induce only pain. Most studies also indicate that thermal stimulation only induces painful sensations. The quality of dental pain can vary. Typically, dentinal stimulation of teeth with healthy pulps induces sharp pain. On the other hand intense heat stimulation can result in dull pain which radiates to a wider area of the face and jaws. This component of the stimulus-induced pain seems to share some characteristics of toothache associated with painful pulpitis. Single fibre recordings of intradental nerve activity in experimental animals have shown that in addition to A-fibres a considerable number of C-type primary afferents innervate the dental pulp. This is in accordance with the results of neuroanatomical studies, which indicate that 70-80% of pulpal axons in human, monkey, dog, and cat teeth are unmyelinated. Intradental A- and C-fibre groups seem to be functionally different and can be activated separately by certain external stimuli. Comparison of the response characteristics of the pulp nerve fibres and the sensations induced from human teeth indicate that: 1) A-fibres are responsible for the sensitivity of dentine and thus for the mediation of the sharp pain induced by dentinal stimulation, 2) Prepain sensations induced by electrical stimulation result from activation of the lowest threshold A-fibres some of which can be classified as A beta-fibres according to their conduction velocities. Comparison of the responses of the A beta- and A delta-fibres indicate that they belong to the same functional group, 3) Intradental C-fibres are activated only if the external stimuli reach the pulp proper. Their activation may contribute to the dull pain induced by intense thermal stimulation of the tooth and to that associated with pulpal inflammation.

Studies on the presence and functional properties of afferent C-fibers in the cat's dental pulp.

The present investigation describes how intradental afferent C-fibers can be identified and characterized in the anaesthetized cat. Functional single fibers innervating the lower canine tooth were recorded from filaments split from the inferior alveolar nerve. Fibers responding to monopolar electrical stimulation of the tooth were classified as slowly and fast conducting according to their conduction velocity (c.v.). The axonal c.v. was determined for 31 slowly conducting fibers by electrical stimulation of the nerve. Sixty-eight percent of these proved to be C-fibers. The slowly conducting fibers had higher activation thresholds, smaller amplitudes and longer durations of the action potentials than the fast conducting fibers. Many of the fast but none of the slowly conducting fibers were repetitively activated by a single stimulus pulse. The highest frequency at which the fibers responded to every stimulus pulse was much lower for the slowly than for the fast conducting fibers. Most of the slowly conducting intradental fibers tested were activated by both hot and cold stimulation of the tooth, by pressure applied to the pulp chamber and by the application of KCl or bradykinin to the pulp. Eight C-fibers responded to mechanical stimulation of the pulp. For some fibers the response magnitude correlated with the stimulus intensity. Many slowly conducting intradental fibers developed an ongoing discharge after heat and pressure stimulation. The results indicate that there exists in the dental pulp of the cat afferent C-fibers that resemble polymodal C-nociceptors. They might be involved in the generation of the dull aching pain present in inflammatory conditions of the pulp. The activation of intradental C-fibers in pulpitis might result either from the elevated pressure and/or by sensitization of the C-fiber endings by inflammatory substances released.

Involvement of supraspinal and spinal segmental alpha-2-adrenergic mechanisms in the medetomidine-induced antinociception.

The effect of systemically administered medetomidine, a selective alpha-2-adrenoceptor agonist, was studied by electrophysiological recordings of the peripherally evoked responses of three different types of sensory neuronal populations in the rat: medial thalamic neurons exclusively responding to mechanical cutaneous stimuli at noxious intensities, spinothalamic tract neurons of the spinal cord responding exclusively or differentially to mechanical cutaneous stimuli at noxious intensities, and low-threshold mechanoreceptive spinal dorsal horn neurons with ascending projections. The neuronal effects were compared with the behavioral data obtained in mechanically and thermally induced nociceptive tail reflex tests in intact and spinal rats. A reversal of the antinociceptive effects was attempted by systemically (1.5 mg/kg, i.p.) or intrathecally (25 micrograms) administered atipamezole, a selective alpha-2-adrenoceptor antagonist. Systemically administered medetomidine produced an atipamezole-reversible, dose-dependent suppressive effect on the evoked responses of nociceptive medial thalamic and spinothalamic tract neurons. A lower dose of medetomidine was needed to suppress significantly (half-maximally) evoked responses of the nociceptive medial thalamic neurons (100 micrograms/kg) than those of the nociceptive spinothalamic tract neurons (300 micrograms/kg). The decrease of evoked responses of the nociceptive spinothalamic tract neurons was accompanied by a decrease in spontaneous activity. The responses of the low-threshold mechanoreceptive projection neurons of the spinal cord were not influenced by medetomidine (30-300 micrograms/kg). The reflex studies with a (anesthetic) medetomidine dose of 300 micrograms/kg indicated that in intact and otherwise drug-free rats, medetomidine produced a significant prolongation of the nociceptive reflex response latency to a tail-pinch and heat; these antinociceptive effects of systemic medetomidine were reversed by systemically and intrathecally applied atipamezole. In spinal rats systemically applied medetomidine (300 micrograms/kg) also produced a significant prolongation of the tail-flick latency, which was reversed by systemically applied atipamezole. The results suggest that a high anesthetic dose of systemically applied medetomidine (300 micrograms/kg) can suppress nociceptive sensory neuronal and reflex responses due to spinal segmental mechanisms through an action on alpha-2-adrenoceptors. This spinal effect is selective to responses of nociceptive neurons, and at least partly postsynaptic as indicated by the concomitant decrease in spontaneous activity. At a lower, subanesthetic (but sedative) dose (100 micrograms/kg) the antinociceptive effect of systemically applied medetomidine can be explained by supraspinal alpha-2-adrenergic mechanisms.

Afferent C fibre innervation of cat tooth pulp: confirmation by electrophysiological methods.

1. The presence of afferent C fibres innervating the lower canine tooth was investigated in Nembutal-anaesthetized cats. 2. Twenty-five single fibres with conduction velocities (CVp) of less than 2.5 m/s, as calculated from the shortest response latency using monopolar electrical stimulation of the tooth, were recorded from the inferior alveolar nerve. In addition, the extradental conduction velocity (CVn) of the fibres was determined by using bipolar electrical stimulation of the trunk of the inferior alveolar nerve. 3. The mean CVp was 1.4 +/- 0.4 m/s (n = 25; range, 0.6-2.4 m/s); the mean CVn was higher, 1.7 +/- 0.9 m/s (n = 25; range, 0.6-4.0 m/s). For 20% of the fibres CVn exceeded 2.5 m/s; these were slowly conducting A delta fibres. For 80% of the fibres, however, the extradental conduction velocity was in the C fibre range. 4. The relationship between CVp (y) and CVn (x) was y = 0.66 + 0.40x, the correlation coefficient being r = 0.85. According to the present results this implies that for a reliable classification of pulpal C fibres (CVn less than or equal to 2.5 m/s) by monopolar tooth stimulation alone, CVp should be less than 1.7 m/s. 5. For twenty-three of the twenty-five fibres, one to three discrete shortenings of the response latency occurred when the intensity of the tooth stimulation was increased. When the nerve trunk itself was stimulated, a constant response latency was measured at all stimulus intensities applied. 6. For twelve fibres tested, the mean rate of electrical stimulation of the tooth, which the response followed with a constant latency, was 4.1 +/- 2.3 Hz (range, 1.5-10.0 Hz). With higher rates of stimulation the response latency increased until the fibres failed to follow each stimulus pulse. 7. Fifteen of the nineteen fibres tested responded to radiant heat stimulation of the tooth they were innervating. The mean temperature threshold was 41.4 +/- 2.7 degrees C (n = 11; range, 37.4 +/- 46.4 degrees C). 8. For eight heat-sensitive pulpal C fibres the receptive field was determined by mechanical stimulation of the exposed pulp tissue. Four C fibres developed a long-lasting on-going discharge after intense mechanical stimulation of the receptive field. 9. The discharge evoked by heat and mechanical stimulation of the tooth occluded the response evoked by simultaneously applied electrical current pulses to the nerve trunk, indicating that the same fibres were activated by both tooth and nerve stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Reflex responses in the digastric and tongue muscles to stimulation of intradental nerves in the cat.

Electrical stimulation of tooth pulp nerves induces the digastric jaw-opening reflex in the cat, apparently due to activation of intradental A-fibres; C-fibres do not seem to be involved. In fact, reflex responses to activation of pulpal C-fibres have not been studied. In the present experiments on anesthetized cats we recorded EMG reflex responses of the digastric and tongue muscles to stimulation of the intact tooth crown, exposed dentine, and the pulp. We used stimuli that selectively activate either A- or C-fibres of the pulp. Slow heating of the tooth and application of capsaicin into the pulp, both procedures known to excite only C-fibres in the pulp, evoked licking movements of the tongue and prolonged EMG-responses in the tongue and, less consistently, digastric muscles. Similar muscle responses were elicited by high intensity electrical current pulses applied to the tooth. At low current intensities only short-duration digastric activation (jaw-opening reflex) was induced. Similar digastric jaw-opening was also evoked by drilling and air-drying of dentine, both stimuli able to activate only intradental A-fibres. These results indicate that activation of both A- and C-type pulp nerve fibres can induce reflectory muscle activation, and further, they support the concept of afferent intradental C-fibre innervation.

Activation of carotid sinus baroreceptors reduces pain sensations evoked by electrical and cold stimulation of human teeth.

Activation of carotid sinus baroreceptors (CSBs) has been shown to have an influence on the perception of pain evoked by electrical stimulation of the skin. The present work was carried out to study to what extent dental pain can be modulated by simultaneous activation of CSBs. In 19 healthy voluntary human subjects, activation of CSBs was induced by application of negative pressure to an air tight collar fitted around the neck of the subjects (neck suction). Dental pain was evoked by electrical stimulation of the tooth (determination of the pain threshold) and by cold stimulation of teeth (ratings of the pain intensity). Neck suction resulted in an elevation of the dental pain thresholds and a reduction of the ratings of the cold-evoked dental pain. The present findings support the suggestion of the interaction of cardiovascular control systems with trigeminal nociceptive systems.

Effect of naloxone on tooth pulp-evoked jaw-opening reflex in the barbiturate-anaesthetized cat.

The threshold of the tooth pulp-evoked jaw-opening reflex was uninfluenced by administration of 0.5 or 5.0 mg kg-1, i.v. naloxone, a specific opioid antagonist, in the barbiturate-anaesthetized cat. Furthermore, facilitatory or inhibitory interactions between two successive tooth pulp-evoked jaw reflex responses were not influenced by naloxone. It is concluded that naloxone-sensitive opioid receptor-mediated mechanisms do not contribute to the modulation of tooth pulp-evoked reflexes by conditioning dental stimuli. Also they do not exert a tonic inhibition on the sensory or motor part of the tooth pulp-driven reflexes. Experiments performed for comparison showed that the non-nociceptive polysynaptic reflex discharge in the flexo-motor neurons of the limb was not influenced by naloxone either.