Physiological properties and morphological characteristics of cutaneous and mucosal mechanical nociceptive neurons with A-δ peripheral axons in the trigeminal ganglia of crotaline snakes

Primary A-δ nociceptive neurons in the trigeminal ganglia of immobilized crotaline snakes were examined by intrasomal recording and injection of horseradish peroxidase in vivo. Thirty-four neurons supplying the oral mucosa or facial skin were identified as A-δ nociceptive neurons which responded exclusively to noxious mechanical stimuli and had a peripheral conduction velocity ranging from 2.6 to 15.4 m/s. These neurons were subdivided into a fast-conducting type (FC-type) and a slowly conducting type (SC-type). Neurons of both types had a receptive field limited to a single spot which responded to pin prick stimulus with a threshold of more than 5 g. The FC-type neurons had a narrow spike followed by a shorter after-hyperpolarization. In contrast, SC-type neurons exhibited a broad spike with a hump on the falling phase and a longer after-hyperpolarization. The diameters of the stem, central and peripheral axons of the FC-type neurons were significantly thicker than those of the SC-type neurons, but there was no statistical difference in the soma size of the two types. Central axons of both types of neurons were thinner than their stem and peripheral axons. Dichotomizing fibers of peripheral axons were observed within the ganglion on 3 neurons. Central axons of the FC-type neurons terminated ipsilaterally in the nucleus principalis, the subnucleus oralis, interpolaris and caudalis and the interstitial nucleus, whereas those of the SC-type neurons generally projected only to the caudal half of the subnucleus interpolaris, subnucleus caudalis and interstitial nucleus ipsilaterally. The present data showed for the first time the physiological and morphological heterogeneity of the primary trigeminal A-δ nociceptive neurons and revealed that the trigeminal nucleus principalis and all the subdivisions of the trigeminal descending nucleus are involved in nociception as relay nuclei, but the subnucleus caudalis and the caudal half subnucleus interpolaris are the essential relay sites of the primary nociceptive afferents supplying the oral mucosa and facial skin. The interstitial nucleus also appears to play an important role in orofacial nociception. © 1993 Wiley-Liss, Inc.     

Evidence for peripheral, but not central modulation of trigeminal cold receptive cells in the rat

The effects of locus coeruleus (LC), periaqueductal grey (PAG) and segmental stimulation (all of which are known to inhibit convergent nociceptive cells), were tested on the activity of cold receptive cells in the trigeminal system of the rat. LC and PAG stimulation from sites which inhibited convergent nociceptive cells had no effect on cells with cold receptive input in the trigeminal nucleus caudalis. Electrical or mechanical segmental stimulation caused suppression of activity in cold receptive trigeminal nucleus neurons. Recording from the trigeminal ganglion showed this suppression to be a property of the primary afferent cold receptors themselves and therefore it is not analogous to the proposed mechanism for the segmental inhibition of convergent nociceptive neurons.     

Descending modulation of visceral nociceptive transmission from the locus coeruleus/subcoeruleus in the rat

The purpose of the present investigation was to examine whether electrical stimulation in the locus coeruleus/subcoeruleus (LC/SC) could modulate visceral pain evoked by noxious colorectal distention (CRD). Experiments were performed on 40 pentobarbital anesthetized male Sprague–Dawley rats. Extracellular potentials of single L₆–S₂ spinal neuron were recorded with a carbon filament electrode. CRD (80 mmHg) was produced by inflating a balloon inside the descending colon and rectum. Electrical stimulation of the LC/SC (30, 50 and 70 μA, 100 Hz, 0.1 ms pulses) was delivered either ipsilaterally or contralaterally. Results showed that for 42/62 (68%) short-latency abrupt (SL-A) neurons, all of the short-latency sustained (SL-S) and long-latency (LL) neurons, LC/SC stimulation produced intensity-dependent attenuation of the CRD-evoked discharge. For 10/62 (16%) SL-A neurons, 6/8 (75%) inhibited (INHIB) neurons LC/SC stimulation increased the evoked discharge, for 10/62 (16%) SL-A neurons and 2/8 (25%) INHIB neurons, the evoked discharges were unaffected by the LC/SC stimulation. LC/SC stimulation also had different effects on the spontaneous activities of these neurons. The effects of LC/SC stimulation were the same both ipsilaterally and contralaterally either for the evoked discharges or for spontaneous activities. Following LC/SC lesions, LC/SC stimulation did not inhibit nociceptive responses, whereas inhibitory effects were observed by stimulation of the intact LC/SC contralateral to the recording site. These data suggest that the transmission of visceral pain was under the control of the centrifugal pathways from the LC/SC.     

Brainstem and spinal pathways mediating descending inhibition from the medullary lateral reticular nucleus in the rat

The lateral reticular nucleus (LRN) in the caudal ventrolateral medulla has been implicated in descending monoaminergic modulation of spinal nociceptive transmission. Experiments were undertaken to examine the organization of pontine and spinal pathways mediating inhibition of the tail-flick (TF) reflex from the LRN in rats lightly anesthetized with pentobarbital. Microinjections of the local anesthetic lidocaine ipsilaterally or bilaterally into the dorsolateral pons blocked stimulation-produced inhibition of the TF reflex from the nucleus locus coeruleus/subcoeruleus (LC/SC), but had no effect on descending inhibition produced by microinjection of glutamate into the LRN. Thus, adrenergic modulation of the TF reflex from the LRN is not mediated by activation of spinopetal noradrenergic neurons in the LC/SC. The funicular course of descending inhibition produced by focal electrical stimulation in the LRN was studied in separate groups of rats by reversibly (local anesthetic blocks) or irreversibly (surgical transection) compromising conduction in the dorsolateral funiculi (DLFs) at the level of the cervical spinal cord. Bilateral lidocaine blocks in the DLFs significantly shortened control TF latencies and more than doubled the intensity of electrical stimulation in the LRN necessary to inhibit the TF reflex (153 +/- 29% increase from control); changes in these parameters produced by unilateral blocks of the DLFs were not statistically significant. Ipsilateral or bilateral transections of the DLFs significantly increased the intensity of electrical stimulation in the LRN to inhibit the TF reflex (110 +/- 24% and 265 +/- 46% from control, respectively). Neither lidocaine blocks nor transections of the DLFs completely blocked the descending inhibitory effects of electrical stimulation in the LRN. The DLFs appear to carry fibers mediating LRN stimulation-produced inhibition of the TF reflex as well as tonic descending inhibition of spinal reflexes. The results of the present study indicate that (1) adrenergic modulation of the nociceptive TF reflex from the LRN does not depend on a rostral loop through the pontine LC/SC, and (2) descending inhibitory influences from the LRN are contained in, but not confined to, the dorsal quadrants of the spinal cord.     

Wind-up of tooth pulp-evoked responses and its suppression in rat trigeminal caudal neurons

Induction and suppression of wind-up were studied in 97 tooth pulp-driven neurons in the trigeminal subnucleus caudalis, using Wistar albino rats anesthetized with urethane and alpha-chloralose. Tooth pulp stimulation applied to an ipsilateral lower incisor evoked early discharges, indicating excitatory inputs from A-delta fibers and subsequent late discharges from C-fiber volleys in caudal neurons. Wind-up was efficiently evoked by stimulation delivered at 0.3-1 Hz, with current intensity sufficient to evoke late discharges. Conditioning stimulation of the arcuate nucleus of the hypothalamus (ARH) suppressed late discharges, including wind-up, without affecting the A-fiber response. Focal cooling of the periaqueductal gray (PAG) abolished the suppression by the ARH and further enhanced the wind-up of the caudal neurons. These results suggest: 1) Temporal summation of depolarization evoked by C-fiber volleys builds wind-up in caudal neurons; 2) ARH stimulation suppresses late discharges by blocking synaptic transmission from C-fiber inputs, and this interrupts prolonged facilitation of the neurons; 3) the ARH is involved in induction of inhibitory controls descending from the PAG to the trigeminal caudalis.     

Adrenalectomy increases reduced nicotinamide adenine dinucleotide phosphate-diaphorase activity in the rat spinal trigeminal subnucleus caudalis

Neurons exhibiting reduced nicotinamide adenine dinucleotide phosphate-diaphorase activity (NADPHd) were quantified at 500 μm rostrocaudal intervals in spinal trigeminal nucleus (Vsp) of adenalectomized (ADX), ADX + corticosterone, and sham-ADX rats 6–12 days after surgery. NADPHd neurons were found predominantly in Vsp subnucleus caudalis (Vc) and in dorsomedial subnucleus oralis. ADX significantly increased the number of NADPHd neurons in superficial laminae of Vc, an effect reversed by chronic corticosterone replacement. ADX effects on NADPHd in superficial laminae of Vc but not in deep laminae of Vc or in the periobex region of Vsp paralleled previously observed sites of ADX enhancement of noxious stimulus-induced Fos-like immunoreactivity. The results indicate that chronic changes in adrenal steroid status regulate NADPHd, a mechanism that may both derive from changes in nitric oxide synthase expression and influence the processing of nociceptive information by central trigeminal neurons.     

Distribution of fos-like immunoreactivity in the caudal brainstem of the rat following noxious chemical stimulation of the temporomandibular joint

Central expression of the protooncogene c-fos was used to examine areas receiving noxious sensory input from the rat temporomandibular joint (TMJ). Fos-like immunoreactivity (Fos-LI) in the caudal brainstem was visualized 2 hours after unilateral injection of the small-fiber-specific excitant /inflammatory irritant mustard oil into the TMJ region. Control animals received injection of either mustard oil into the subcutaneous fascia overlying the masseter muscle or mineral oil vehicle into the TMJ region. In all groups, Fos-LI was consistently observed ipsilaterally in the spinal trigeminal nucleus and cervical dorsal horn and, bilaterally, in the nucleus of the solitary tract and. the ventrolateral medulla. The expression of Fos-LI ipsilaterally in the paratrigeminal nucleus was variable. Within the trigeminal sensory complex, Fos-LI was restricted to subnucleus caudalis and the caudal portions of subnucleus interpolaris near the level of the obex. Approximately 12% of Fos-LI cells in subnucleus caudalis and in the cervical dorsal horn were found in laminae III-VI. Compared to TMJ mustard oil injection, mineral oil injection produced less Fos-LI at all rostrocaudal levels, whereas subcutaneous mustard oil injection produced less Fos-LI in caudal subnucleus caudalis but similar amounts in the cervical dorsal horn. Neither of these injections yielded significant ipsilateral responses in subnucleus caudalis, indicating that Fos-LI in this region following TMJ mustard oil injection could be ascribed solely to small-fiber stimulation in the deep TMJ region. The wide rostrocaudal distribution of Fos-LI within the caudal brainstem reflects the distribution of TMJ-responsive nociceptive neurons that may underlie the spread and referral of pain from the TMJ region. © 1995 Wiley-Liss, Inc.     

Inhibition of spinal nociceptive transmission from the midbrain, pons and medulla in the rat: activation of descending inhibition by morphine, glutamate and electrical stimulation

It is generally believed that morphine activates a descending system(s) of inhibition, an effect contributing significantly to the analgesia produced. There has arisen, however, considerable controversy on this point. To address whether morphine inhibits spinal nociceptive transmission when given into the brainstem, the effects of focal electrical stimulation and monosodium S-glutamate (Glu) given in the periaqueductal gray (PAG), the locus coeruleus/subcoeruleus (LC/SC) and/or the nucleus raphe magnus (NRM) on spinal unit responses to noxious heating (50 °C) of the skin were examined and compared with effects produced by morphine (Mor). Focal electrical stimulation in 46 sites in the midbrain, dorsolateral pons and ventromedial medulla reliably inhibited unit responses to noxious heating of the skin (mean 34% of control). Microinjections of Glu (50 nmol, 0.5 μl) were made into 17 sites in the midbrain, 10 sites in the LC/SC and 11 sites in the NRM, inhibiting unit responses to a mean 57% at 22 of the 38 sites of microinjection. Mor (10–20 μg, 0.5 μl) was microinjected into 15 sites in the midbrain, 13 sites in the LC/SC and 11 sites in the NRM, inhibiting unit responses to heat to 63% of control at 24 sites of microinjection. The effects of morphine were shown to be receptor specific by antagonism with naloxone administered either intravenously or into the brainstem at the same site of microinjection as morphine. In 31 sites in the midbrain, dorsolateral pons and ventromedial medulla, microinjections of both Mor and Glu into the same sites attenuated unit responses to heating of the skin to a mean 77% and 71% of control, respectively. The results support the hypothesis that Mor acts supraspinally to modulate spinal nociceptive transmission by activating an endogenous descending inhibitory system(s). Focal electrical stimulation, glutamate and morphine modulated spinal nociceptive transmission by activation of descending inhibitory systems whose cell bodies of origin are in the PAG, the LC/SC or the NRM.     

Stimulation of the cerebral peduncles modulates tooth pulp-evoked firing of trigeminal caudalis neurons

Unit activity was recorded from trigeminal subnucleus caudalis neurons in immobilized, lightly anesthetized (Nembutal) cats following bipolar electrical stimulation of the canine tooth pulp. Electrical stimuli applied to the cerebral peduncles through stereotaxically placed coaxial electrodes discharged or inhibited most tooth pulp-activated nucleus caudalis (relay and nonrelay) neurons.     

Inhibition of hyperactive trigeminal subnucleus caudalis neurons after experimental trigeminal rhizotomy in response to thalamic sensory relay nucleus stimulation*

The effects of thalamic sensory relay nucleus stimulation on the single neuron activity and field potentials within the trigeminal subnucleus caudalis, which is a trigeminal equivalent of the dorsal horn were investigated in intact cats as well as in cats subjected to retro-Gasserian rhizotomy 1-6 months before the experiments. inhibition of nociceptive neural activity and a positive field potential were evoked by thalamic stimulation in the dorsal horn of the intact animals. A positive field potential followed double pulse stimulation with frequencies ranging up to approximately 50 Hz. The inhibitory periods ranged from 60 to 100 ms. Train pulse stimulation with frequencies ranging from 30 to 50 Hz produced long-lasting inhibition of nociceptive neural activity and a positive shift of the field potentials. Essentially identical inhibition of abnormal neural hyperactivity occurring in the rhizotomized dorsal horn was observed. The positive field potential corresponding to this inhibition also displayed characteristics similar to the field potential seen in the intact dorsal horn. These data indicate that the pathways involved in the inhibitory responses induced by thalamic. sensory relay nucleus stimulation, unlike some other pain inhibitory systems, can exert their influence even to the dorsal horn which has undergone reorganization of neural circuits after rhizotomy.     

Convergence patterns of afferent information from the temporomandibular joint and masseter muscle in the trigeminal subnucleus caudalis

Convergence patterns of afferent information from the temporomandibular joint (TMJ) and the masseter muscle (Mm) in the trigeminal subnucleus caudalis in response to natural stimulation were examined in anesthetized rats for a better understanding of masticatory pain phenomena. All neurons tested (135) could be placed in one of the following three classes according to their responsiveness to natural stimulation in the TMJ and/or the Mm: Class I neurons, excited by only innocuous stimuli; Class II neurons, excited by only noxious stimuli; Class III neurons, excited by both. Afferent inputs from the TMJ and the Mm converged on 108 (80%) of the 135 neurons. Of these convergent neurons, 79% received nociceptive information from the TMJ and/or the Mm. The results suggest that convergent caudalis neurons that receive nociceptive information from the TMJ and/or the Mm may be important to referred pain associated with dysfunction of the masticatory system.     

Inhibition of hyperactive trigeminal subnucleus caudalis neurons after experimental trigeminal rhizotomy in response to thalamic sensory relay nucleus stimulation

The effects of thalamic sensory relay nucleus stimulation on the single neuron activity and field potentials within the trigeminal subnucleus caudalis, which is trigeminal equivalent of the dorsal horn were investigated in intact cats as well as in cats subjected to retro-Gasserian rhizotomy 1-6 months before the experiments. Inhibition of nociceptive neural activity and a positive field potential were evoked by thalamic stimulation in the dorsal horn of the intact animals. A positive field potential followed double pulse stimulation with frequencies ranging up to approximately 50 Hz. The inhibitory periods ranged from 60 to 100 ms. Train pulse stimulation with frequencies ranging from 30 to 50 Hz produced long-lasting inhibition of nociceptive neural activity and a positive shift of the field potentials. Essentially identical inhibition of abnormal neural hyperactivity occurring in the rhizotomized dorsal horn was observed. The positive field potential corresponding to this inhibition also displayed characteristics similar to the field potential seen in the intact dorsal horn. These data indicate that the pathways involved in the inhibitory responses induced by thalamic sensory relay nucleus stimulation, unlike some other pain inhibitory systems, can exert their influence even to the dorsal horn which has undergone reorganization of neural circuits after rhizotomy.     

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.     

Central terminals of orofacial primary afferents and NADPH-diaphorase activity in the trigemino–solitary complex of rats

Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) activity and the central terminal fields of branches of the mandibular and chorda tympani nerves were visualized histochemically at the same time using transganglionic transport of wheat germ agglutinin conjugated with horseradish peroxidase. The blue NADPH-d-positive neurons comprised a sparse network in the dorsomedial spinal trigeminal subnucleus oralis and a dense one in the rostral lateral division of the nucleus of the solitary tract. In the subnucleus caudalis, most labeled neurons were in the superficial zone, and smaller numbers were in the magnocellular zone. The NADPH-d-positive neurons in the subnucleus oralis and the nucleus of the solitary tract overlapped mostly with the transganglionically labeled terminal field from the lingual nerve, partly with the terminal field from the inferior alveolar and chorda tympani nerves, and rarely with the terminal field from the mental nerve. The NADPH-d-positive neurons in the dorsomedial paratrigeminal nucleus and subnucleus caudalis overlapped mostly with the terminal field from the lingual nerve, partly with the terminal field from the inferior alveolar and mental nerves and never with the terminal field from the chorda tympani. A statistically significant reduction in the number of NADPH-d-positive neurons was seen bilaterally in subnucleus oralis and the nucleus of the solitary tract when the lingual nerve was transected. Inflammatory insults to the lingual nerve or tooth pulps significantly increased the number of NADPH-d-positive neurons in subnucleus oralis, the nucleus of the solitary tract, and subnucleus caudalis. These results show that the NO/cyclic GMP system in the trigeminal and solitary nuclei is differentially regulated trans-synaptically by trigeminal afferents depending on the nucleus and sensory modality.     

Periaqueductal gray inhibition of trigeminal subnucleus caudalis unitary responses evoked by dentine and nonnoxious facial stimulation

The possible pain inhibitory effects of periaqueductal gray (PAG) stimulation were investigated in cats anesthetized with Nembutal and immobilized with Flaxedil. Unitary responses evoked by electrical stimulation of the upper canine dentine and by cutaneous facial noxious and nonnoxious stimuli were recorded extracellularly from the trigeminal subnucleus caudalis. A bipolar electrode was introduced into the PAG to test the effects of PAG excitation on the trigeminal response to dentine (TRED) and cutaneous nonnoxious stimulation. In some experiments, a similar electrode was lowered into the contralateral posterior thalamus to study the antidromic activation of subnucleus caudalis cells and the effects of thalamic stimulation on the TRED. Dentine stimulation evoked brief (6- to 15-ms) bursts of 1 to 10 spikes with 3- to 25-ms latencies. Most units (88%) were also activated by cutaneous facial stimulation. Stimulation of the posterior thalamus had no effect on the TRED or on responses to cutaneous stimulation, but activated antidromically 10% of the units. In 71% of the units PAG stimulation inhibited the TRED. In some of those cases (12%), the inhibitory effect persisted 30- to 60 s. The PAG stimulation could produce paradoxical effects, potentiating the TRED evoked by threshold intensity and inhibiting the TRED elicited by suprathreshold stimulation. About one-half the PAG points evoked detectable effects. Their location had no clear topographical distribution, although ventral sites were more potent than dorsal sites. Responses evoked by nonnoxious facial stimulation were also inhibited by the PAG.     

Effect of spinal norepinephrine depletion on descending inhibition of the tail flick reflex from the locus coeruleus and lateral reticular nucleus in the rat

The lateral reticular nucleus (LRN) and locus coeruleus-subcoeruleus (LC/SC), brainstem structures which overlap the A1 and A6 noradrenergic nuclei respectively, have been implicated in descending modulation of spinal nociceptive transmission. The present studies were designed to examine the role of norepinephrine (NE) in the mediation of inhibition of the nociceptive tail flick reflex produced by focal electrical stimulation in the LRN and LC/SC. Spinal NE was depleted by intrathecal administration of 6-hydroxydopamine (6-OHDA; 20 micrograms) and the threshold electrical stimulation in the LRN and the LC/SC necessary to inhibit the tail flick reflex in lightly pentobarbital-anesthetized rats was determined 9 and 14 days later. Despite a significant depletion (greater than 85%) of lumbar spinal cord NE content, there was no significant change in the tail flick inhibitory stimulation thresholds in the LRN or LC/SC. NE depletion did, however, potentiate the elevation in the inhibitory stimulation threshold in the LRN produced by intrathecal administration of the alpha 2-adrenoceptor antagonist, yohimbine, suggesting that upregulation of spinal adrenoceptors had occurred following 6-OHDA treatment. Adrenoceptor up-regulation was examined quantitatively by characterizing the dose-dependent antinociceptive potency of the selective alpha 2-adrenoceptor agonist clonidine 3, 7, 10, and 14 days following 6-OHDA administration, and analysis of [3H]rauwolscine binding to lumbar spinal cord 9 days following administration of the neurotoxin. The development of supersensitivity, defined as the leftward parallel shift of the dose-response curves for clonidine administered intrathecally, corresponded to the time course of NE depletion following 6-OHDA treatment on the days tested. Binding of [3H]rauwolscine to lumbar spinal cord revealed an elevation in the estimated Bmax without a change in the estimated Kd of the high affinity binding component 9 days following 6-OHDA administration. This study demonstrates that spinal adrenoceptor denervation supersensitivity develops rapidly following intrathecal administration of 6-OHDA and compensates for the selective destruction of spinal noradrenergic nerve terminals. Thus, the absence of effect of NE depletion on the tail flick inhibitory stimulation threshold in the LRN and the LC/SC does not argue against the hypothesis that spinopetal NE-containing neurons in these brainstem loci are involved in modulation of spinal nociceptive transmission.     

c-fos induction in the subnucleus oralis following trigeminal nerve stimulation

Neurons with c-Fos protein-like immunoreactivity (fos-neurons) were examined in the rostral parts of the brainstem sensory trigeminal nuclear complex following intense electrical stimulation of the trigeminal nerves and noxious mechanical stimulation of the trigeminal receptive fields. Stimulation of all the examined nerves and receptive fields induced some fos-neurons at the medial edge of the subnucleus interpolaris but not in the principal sensory trigeminal nucleus. Stimulation of the primary neurons innervating the intraoral structures but not facial skin induced fos-neurons in the ipsilateral subnucleus oralis. These oralis fos-neurons were located in the dorsomedial nucleus that contained calcitonin gene-related peptide-like immunoreactivity. The oralis fos-neurons are considered to be involved in the processing of intraoral nociceptive signals.     

Evidence for subnucleus interpolaris in craniofacial muscle pain mechanisms demonstrated by intramuscular injections with hypertonic saline

The subnucleus interpolaris (Vi) has been identified as a major recipient for trigeminal ganglionic input from jaw muscles, and contains neurons with nociceptive properties similar to those in the subnucleus caudalis (Vc). Therefore, Vi may be another important site for processing craniofacial muscle nociception. The aims of present study were to define functional properties of Vi neurons that receive input from masseter muscle afferents by characterizing their responses to electrical, mechanical, and to chemical stimulation of the muscle. Ninety cells were identified as masseter muscle units in 11 adult cats. Most of these units (79%) received additional inputs from orofacial skin. Following the intramuscular injection of 5% hypertonic saline, 49% of the cells showed a significant modulation of either the resting discharge and/or responses to innocuous mechanical stimulation on their cutaneous receptive fields (RFs). The most common response to saline injection was an induction or facilitation of resting discharge which declined as an exponential decay function, returning to pre-injection level within 3-4 min. Forty-five percent of the muscle units that were tested with mechanical stimulation (13/29) showed a prolonged inhibition of mechanically-evoked responses. In most cases (8/13), the inhibitory response was accompanied by initial facilitation. The observations that Vi contained a population of neurons that receive small diameter muscle afferent inputs, responded to noxious mechanical stimulation on the muscle and to a chemical irritant that is known to produce pain in humans provide compelling evidence for the involvement of Vi in craniofacial muscle pain mechanisms.     

A possible synaptic configuration underlying coeruleospinal inhibition of visceral nociceptive transmission in the rat

A synaptic arrangement underlying descending inhibition from the locus coeruleus/subcoeruleus (LC/SC) on visceral nociceptive transmission in the spinal cord was investigated in the anesthetized rat. Extracellular recordings were made from the L₆-S₂ segmental level using a carbon filament glass microelectrode (4–6 MΩ). Colorectal distention (CRD) was produced by inflating a balloon inside the descending colon and rectum. All neurons tested responded to both CRD and to cutaneous pinch (a force of 613 g/mm²), indicating that nociceptive signals from visceral organs and nociceptive signals from the cutaneous receptive field converge on a single neuron. These neurons were divided into two groups based on their response to CRD: short latency-abrupt and short latency-sustained neurons. Electrical stimulation of the LC/SC (30 or 50 μA, 100 Hz, 0.1 ms pulses) inhibited both CRD-evoked and cutaneous pinch-evoked responses in short latency-abrupt and short latency-sustained neurons. When graded CRD (20, 40, 60, and 80 mmHg) was delivered, LC/SC stimulation produced a reduction in slope of the linear CRD intensity-response magnitude curve without a change in the response threshold in both short latency-abrupt (n = 42) and short latency-sustained neurons (n = 11). This result suggests that coeruleospinal inhibition of visceral nociceptive transmission is due to a synaptic configuration in which inhibitory and excitatory terminals are in close spatial proximity, including presynaptic inhibition.     

Cells of origin of the trigeminohypothalamic tract in the rat

Recent studies have demonstrated that a large number of spinal cord neurons convey somatosensory and visceral nociceptive information directly from cervical, lumbar, and sacral spinal cord segments to the hypothalamus. Because sensory information from head and orofacial structures is processed by all subnuclei of the trigeminal brainstem nuclear complex (TBNC) we hypothesized that all of them contain neurons that project directly to the hypothalamus. In the present study, we used the retrograde tracer Fluoro-Gold to examine this hypothesis. Fluoro-Gold injections that filled most of the hypothalamus on one side labeled approximately 1,000 neurons (best case = 1,048, mean = 718 ± 240) bilaterally (70% contralateral) within all trigeminal subnuclei and C1–2. Of these neurons, 86% were distributed caudal to the obex (22% in C2, 22% in C1, 23% in subnucleus caudalis, and 18% in the transition zone between subnuclei caudalis and interpolaris), and 14% rostral to the obex (6% in subnucleus interpolaris, 4% in subnucleus oralis, and 4% in subnucleus principalis). Caudal to the obex, most labeled neurons were found in laminae I–II and V and the paratrigeminal nucleus, and fewer neurons in laminae III–IV and X. The distribution of retrogradely labeled neurons in TBNC gray matter areas that receive monosynaptic input from trigeminal primary afferent fibers innervating extracranial orofacial structures (such as the cornea, nose, tongue, teeth, lips, vibrissae, and skin) and intracranial structures (such as the meninges and cerebral blood vessels) suggests that sensory and nociceptive information originating in these tissues could be transferred to the hypothalamus directly by this pathway. J. Comp. Neurol. 400:125–144, 1998. © 1998 Wiley-Liss, Inc.