Takayoshi Tabata

Induction of histidine decarboxylase in skeletal muscle in mice by electrical stimulation, prolonged walking and interleukin-1

1 In normal non‐exercised skeletal muscles in mice, the activity of histidine decarboxylase (HDC), the enzyme which forms histamine, was very low. 2 HDC activity in the quadriceps femoris muscle was markedly elevated following contractions evoked by even a few minutes of direct electrical stimulation, peaking at 8‐12 h following contraction lasting 10 min, and gradually decreasing during the 24 h following contraction. The elevation in HDC activity depended on the duration and strength of stimulation. 3 Direct electrical stimulation induced a quantitatively similar elevation of HDC activity in the muscles of mast‐cell‐deficient mice (W/Wv mice). 4 Prolonged walking at a speed of 6 m min−1 for up to 6 h with a 30 min rest period at 3 h also elevated muscle HDC activity, the magnitude of the elevation being related to the duration of the walking. Repeated exercise (training) for several days diminished the elevation of muscle HDC activity induced by walking. In contrast, starvation augmented the elevation of muscle HDC activity induced by walking. 5 Intraperitoneal injection of interleukin‐1β (IL‐1β) also elevated muscle HDC activity in a dose‐dependent manner, as little as 1 μg kg−1 of IL‐1 producing a significant elevation of muscle HDC activity. 6 IL‐1β was immunohistochemically detected in normal non‐exercised quadriceps femoris muscle. We could not detect a significant increase in IL‐1β after exercise in the muscle or in serum: it may be below the level of detection. 7 On the basis of these results, together with those reported previously and the known actions of histamine, we propose that an elevation of HDC activity and generation of histamine occur in skeletal muscle following muscle contraction possibly as a result of induction by IL‐1β and that the histamine may be involved in fatigue in skeletal muscle as part of a defence mechanism preventing damage to the muscle.

Pulpal and cutaneous inputs to somatosensory neurons in the parabrachial area of the cat

The majority of somatosensory neurons recorded from the mesencephalic parabrachial area and pontine parabrachial nucleus of the cat responded exclusively to noxious mechanical stimuli to the skin. Their receptive fields were very large. Two-thirds of the neurons tested responded to electrical stimulation of the tooth pulp. These results suggest that neurons in this area have extensive convergence of spinal and trigeminal inputs, and contribute to the affective or autonomic aspects of pain.

Response fields of the periodontal mechanosensitive units in the superior alveolar nerve of the cat

Response properties of periodontal mechanoreceptor primary afferent fibers recorded from the superior alveolar nerve were studied in the cat. The left maxillary canine tooth was stimulated manually in 8 directions and/or in 24 directions in the horizontal plane by a specially designed stimulator. The responses of 328 slowly adapting units observed were affected by the direction of stimulus. These units were classified into three groups according to the shape of the response field: a broad type (more than 180 degrees), a medium type (90 degrees to 180 degrees), and a narrow type (less than 90 degrees). The groups contained 27 units (8.2%), 284 units (86.6%), and 17 units (5.2%), respectively, and the remaining 10 units (10.0%) were unclassified. The shape of each response field was little changed by changes in the stimulus intensity. Every response field investigated showed a unimodal distribution. These results were different from those of Mei et al. (1975) who reported that the response fields of units recorded from a Gasserian ganglion had generally consisted of two parts.

Response properties of periodontal mechanosensitive fibers in the superior dental nerve of the cat

Periodontal mechanosensitive units were detected as single nerve fibers from the anterior branches of five cats, and their receptive fields and optimal stimulus directions were examined. Of 801 units detected, 759 units (95%) responded to movement of only one tooth (single-tooth unit), and 42 units (5%) responded to movement of two or three teeth (multitooth unit). Eighty percent of the single-tooth units were of the sustained type which discharged during more than 1 s to a long-lasting pressure applied to the tooth, and 20% were of the transient type which adapted in less than 1 s to the pressure. The majority (93%) of the sustained type exhibited directional selectivity to stimulation, but only 35% of the transient type showed it. More than half of the single-tooth units had their receptive fields in the canine tooth, stimulation of which produced the largest mass discharge in the nerve bundle. The optimal stimulus direction for many single-tooth units was the same as that for the mass discharge in the nerve bundle. The receptive fields of the multitooth units were observed mainly in the incisor teeth adjacent to each other.

Possible Involvement of Histamine in Muscular Fatigue in Temporomandibular Disorders: Animal and Human Studies

As an approach to clarifying the molecular basis of pain and fatigue in muscles involved in temporomandibular disorders, we examined the activity of histidine decarboxylase (HDC), the enzyme which forms histamine, in the masseter muscles of mice. In the resting muscle, HDC activity was very low. Direct electrical stimulation of the muscle markedly elevated HDC activity. HDC activity rose within 3 hrs of the electrical stimulation, peaked at 6 to 8 hrs, and then gradually declined. Intraperitoneal injection of a small amount of interleukin-1 (IL-1) (from 1 to 10 μg/kg) produced a similar elevation of HDC activity in the masseter muscle. We also examined the effect of an antihistamine, chlorphenylamine (CP), on temporomandibular disorders in humans and compared it with that of an antiinflammatory analgesic, flurbiprofen (FB). Two groups received one or the other of the drugs daily for 7 days, and they were asked about their signs and symptoms before and after the treatment. A positive evaluation of their treatment was made by 74% of the CP group, but by only 48% of the FB group. Although the effects of CP on the limitation of mouth-opening and on joint noise were negligible, about 50% of the CP group answered positively concerning the drugs effect on spontaneous pain or pain induced by chewing or mouth-opening. The positive evaluation for CP (50%) in relieving associated symptoms (headache or shoulder stiffness) was significantly greater than for FB (13%). FB showed effectiveness similar to but sometimes weaker than that of CP on several symptoms. On the basis of these and previous results and the known actions of histamine, we propose that the histamine newly formed following the induction of HDC activity, which is itself mediated by IL-1, may be involved in inducing pain and, possibly, stiffness in muscles in temporomandibular disorders.

Response properties of the periodontal mechanosensitive neurons in the trigeminal main sensory nucleus of the cat

SummaryPeriodontal mechanosensitive units (PM units) were recorded from the trigeminal main sensory nucleus (Vms) of the cat. The receptive fields of PM units were arranged from mandibular to maxillary divisions dorso-ventrally. The majority of PM units were single tooth units responsive to the canine tooth. They were directionally selective and had sustained responses to pressure applied to the tooth. The optimal stimulus direction of maxillary and mandibular PM units when the canine tooth was stimulated was single and it was oriented predominantly in the caudio-medial or rostrolateral direction. The threshold intensity of canine tooth stimulation was less than 0.05 N in most of the units. These findings indicate that the response properties of PM units in the Vms resemble fairly closely those of the primary afferent nerves arising from the periodontal mechanoreceptors.

PHYSIOLOGICAL PROPERTIES OF PERIODONTAL MECHANOSENSITIVE NEURONES IN THE TRIGEMINAL (GASSERIAN) GANGLION OF THE RAT

Periodontal mechanosensitive (PM) primary afferent neurones were recorded from the rat trigeminal ganglion and their response to mechanical tooth stimulation studied. The majority (95%) of PM afferents were single-tooth units and most were sensitive to mechanical stimulation of the incisor. They had a sustained response to pressure applied to the tooth, and showed a directional selectivity to the stimulation. Only a small number (5%) of units were multi-tooth sensitive; their receptive fields were restricted to the molars. When the incisor was stimulated mechanically in 12 directions in a plane perpendicular to the axis of the tooth crown, the predominant response fields of the PM units were of the medium type (90-180 degree response angle) or the broad type (180-360 degrees). Each unit had single optimal stimulus direction oriented predominantly in the rostrocaudal or caudorostral direction. About 60% of the PM units responded to tooth stimulation at irregular spike intervals, whereas the remaining 40% fired at relatively regular intervals. When the tooth was stimulated at a force of 0.05 N, the mean spike interval and rate of spike-interval fluctuation [percentage of the standard deviation (SD) of the interval distribution to the mean interval (mean); SD/mean x 100] were 29.2 ms and 38.1% for the regular-interval units, and 15.1 ms and 8.8% for the irregular-interval ones. The mean spike interval of the regular units was significantly longer than that of the irregular ones.

Response properties of slowly and rapidly adapting periodontal mechanosensitive neurones in the primary somatosensory cortex of the cat

Periodontal mechanosensitive neurones in the primary somatosensory (SI) cortex are classified as either slowly or rapidly adapting. The responses of cortical neurones and their projection pathways were studied using mechanical and electrical stimulation of the teeth and electrical stimulation of the thalamic posteromedial ventral (VPM) nuclei and contralateral SI cortex. A total of 247 periodontal mechanosensitive units were recorded from the SI cortex in 35 anaesthetized cats, distributed mainly in area 3b: 14% were slowly adapting and 86% rapidly adapting units; 62% of the slowly adapting and 9% of the rapidly adapting units were single-tooth units sensitive to stimulation of only one tooth. The incidence of slowly adapting units with an ipsilateral receptive field was almost equal to that of slowly adapting units with a contralateral receptive field, and more than half of the units were directionally selective to mechanical tooth stimulation. The majority of rapidly adapting units had their receptive field in the contralateral teeth and were directionally non-selective to tooth stimulation. The latencies of the cortical responses of the slowly and rapidly adapting units were 7.3 and 10.7 ms, respectively, on electrical stimulation of the contralateral teeth, and 1.8 and 2.0 ms, respectively, on electrical stimulation of the ipsilateral VPM nucleus. From these findings, it is inferred that slowly adapting neurones are useful for discriminating the tooth stimulated, the stimulus direction, the stimulus intensity and the change of pressure applied to the tooth, while rapidly adapting neurones could function to signal initial contact with food or the opposing teeth.

Physiological properties of sensory neurons of the interstitial nucleus in the spinal trigeminal tract.

Neurons were recorded from the interstitial nucleus of the spinal trigeminal tract. They were all nociceptive specific and some projected to the parabrachial area. These data suggest that this nucleus can be regarded as a rostral extension of lamina I of trigeminal subnucleus caudalis.

DISTRIBUTION OF TRIGEMINAL SENSORY NUCLEUS NEURONS PROJECTING TO THE MESENCEPHALIC PARABRACHIAL AREA OF THE CAT

Horseradish peroxidase (HRP) retrograde tracing experiments in the cat demonstrated projections from the trigeminal sensory nuclei to the mesencephalic parabrachial area (PBA), which is located ventral to the inferior colliculus and dorsal to the brachium conjunctivum and includes the nucleus cuneiformis and the most lateral part of the periaqueductal gray. After HRP injection into the mesencephalic PBA, HRP-labeled neuronal cell bodies in the trigeminal sensory nuclei were mainly distributed in the interpolar and caudal spinal trigeminal nuclei (Vi and Vc) bilaterally with a clear-cut contralateral dominance. In Vi, HRP-labeled neurons were mainly distributed in the lateral and medial border regions. In Vc, labeled neurons were located mainly in laminae I and V.