Differential effects of morphine on corneal-responsive neurons in rostral versus caudal regions of spinal trigeminal nucleus in the rat

The initial processing of corneal sensory input in the rat occurs in two distinct regions of the spinal trigeminal nucleus, at the subnucleus interpolaris/caudalis transition (Vi/Vc) and in laminae I-II at the subnucleus caudalis/spinal cord transition (Vc/C1). Extracellular recording was used to compare the effects of morphine on the evoked activity of corneal-responsive neurons located in these two regions. Neurons also were characterized by cutaneous receptive field properties and parabrachial area (PBA) projection status. Electrical corneal stimulation-evoked activity of most (10/13) neurons at the Vi/Vc transition region was increased [146 +/- 16% (mean +/- SE) of control, P < 0.025] after systemic morphine and reduced after naloxone. None of the Vi/Vc corneal units were inhibited by morphine. By contrast, all corneal neurons recorded at the Vc/C1 transition region displayed a naloxone-reversible decrease (55 +/- 10% of control, P < 0.001) in evoked activity after morphine. None of 13 Vi/Vc corneal units and 7 of 8 Vc/C1 corneal units tested projected to the PBA. To determine if the Vc/C1 transition acted as a relay for the effect of intravenous morphine on corneal stimulation-evoked activity of Vi/Vc units, morphine was applied topically to the dorsal brain stem surface overlying the Vc/C1 transition. Local microinjection of morphine at the Vc/C1 transition increased the evoked activity of 4 Vi/Vc neurons, inhibited that of 2 neurons, and did not affect the remaining 12 corneal neurons tested. In conclusion, the distinctive effects of morphine on Vi/Vc and Vc/C1 neurons support the hypothesis that these two neuronal groups contribute to different aspects of corneal sensory processing such as pain sensation, autonomic reflex responses, and recruitment of descending controls.     

Spinal cholinergic and monoamine receptors mediate the antinociceptive effect of morphine microinjected in the periaqueductal gray on the rat tail, but not the feet

The antinociceptive effects of morphine (5 micrograms) microinjected into the ventrolateral periaqueductal gray were determined using both the tail flick and the foot withdrawal responses to noxious radiant heating in lightly anesthetized rats. Intrathecal injection of appropriate antagonists was used to determine whether the antinociceptive effects of morphine were mediated by alpha 2-noradrenergic, serotonergic, opioid, or cholinergic muscarinic receptors. The increase in the foot withdrawal response latency produced by microinjection of morphine in the ventrolateral periaqueductal gray was reversed by intrathecal injection of the cholinergic muscarinic receptor antagonist atropine, but was not affected by the alpha 2-adrenoceptor antagonist yohimbine, the serotonergic receptor antagonist methysergide, or the opioid receptor antagonist naloxone. In contrast, the increase in the tail flick response latency produced by morphine was reduced by either yohimbine, methysergide or atropine. These results indicate that microinjection of morphine in the ventrolateral periaqueductal gray inhibits nociceptive responses to noxious heating of the tail by activating descending neuronal systems that are different from those that inhibits the nociceptive responses to noxious heating of the feet. More specifically, serotonergic, muscarinic cholinergic and alpha 2-noradrenergic receptors appear to mediate the antinociception produced by morphine using the tail flick test. In contrast, muscarinic cholinergic, but not monoamine receptors appear to mediate the antinociceptive effects of morphine using the foot withdrawal response.     

Dopamine receptor antagonists in the nucleus accumbens attenuate analgesia induced by ventral tegmental area substance P or morphine and by nucleus accumbens amphetamine

In the present study, we examined the effects of dopamine (DA) receptor antagonists infused into the nucleus accumbens septi (NAS) on analgesia induced by intra-ventral tegmental area (VTA) infusions of the substance P (SP) analog, DiMe-C7 or morphine and intra-NAS infusions of amphetamine. Rats received intra-NAS infusions of either the mixed DA receptor antagonist flupenthixol (1.5 or 3.0 microg/0.5 microl/side; DiMe-C7 only), the DA D1/D5 receptor antagonist SCH 23390 (0.1 microg/0.5 microl/side; DiMe-C7 only) or the DA D2-type receptor antagonist raclopride (1.0, 3.0 or 5.0 microg/0.5 microl/side). Ten minutes later, rats received intra-VTA infusions of DiMe-C7 (3.0 microg/0.5 microl/side) or morphine (3.0 microg/0.5 microl/side) or intra-NAS infusions of amphetamine (2.5 microg/0.5 microl/side). Animals were then administered the formalin test for tonic pain. Intra-NAS raclopride prevented analgesia induced by intra-VTA DiMe-C7, intra-VTA morphine and intra-NAS amphetamine. Similarly, intra-NAS flupenthixol or SCH 23390 attenuated the analgesia induced by intra-VTA DiMe-C7. These findings suggest that tonic pain is inhibited, at least in part, by enhanced DA released from terminals of mesolimbic neurons. Furthermore, the evidence that SP and opioids in the VTA mediate stress-induced analgesia suggests that the pain-suppression system involving the activation of mesolimbic DA neurons is naturally triggered by exposure to stress, pain or both.     

Morphine application to peripheral tissues modulates nociceptive jaw reflex

This study assessed the effect of peripherally applied opioids on the electromyographic activity reflexly evoked in digastric and masseter muscles by injection of the small-fiber excitant and inflammatory irritant mustard oil (MO) into the temporomandibular joint. In 39 anaesthetized rats, local pretreatment of joint tissues with morphine (15 nmol) significantly depressed the jaw muscle responses compared with saline, and the depression was antagonized by simultaneous local injection of the opiate antagonist naloxone (2.7 nmol); systemic morphine pretreatment (15 nmol, i.v.) did not influence the muscle responses. The naloxone-reversible depression of the MO-evoked muscle responses by local, but not systemic morphine, supports the presence of peripheral opioid receptors that may have a role in modulating nociceptive responses.     

Differential expression of Fos protein after transection of the rat infraorbital nerve in the trigeminal nucleus caudalis

To determine the effects of nerve injury on Fos expression, temporal and spatial distributions of Fos-positive neurons in the trigeminal nucleus caudalis were examined after tissue injury for isolation of the infraorbital nerve as controls and transection of this nerve as well as noxious chemical stimulation by formalin injection in adult rats. Fos immunoreactivity was markedly elevated in laminae I and II of the only ipsilateral nucleus caudalis 2 h after these surgical procedures and noxious chemical stimulation. The distributions of Fos-positive neurons were restricted rostro-caudally following formalin injection and tissue injury compared to transection of the infraorbital nerve. One day after tissue injury and nerve transection, however, Fos-positive neurons were distributed bilaterally in laminae III and IV extending rostro-caudally and medio-laterally in this nucleus, and this persisted over the 2-week study period. The number of Fos-positive neurons in the side ipsilateral to nerve transection was markedly less than that in the contralateral side whereas positive neurons in the tissue injured rats were distributed symmetrically along the rostro-caudal axis. There was no difference in the contralateral sides between nerve transection and tissue injury groups. The rostro-caudal level showing reduction in Fos expression corresponded roughly to the sites of central termination of the injured nerve in this nucleus, suggesting a role for the primary afferents in the reduction of Fos expression in laminae III and IV neurons of the ipsilateral nucleus caudalis.     

Excitation of hypothalamic nucleus arcuatus neuron induced decrease of plasma sialic acid level in rats

The effect of sodium glutamate (Glu) on plasma sialic acid (SA) level was studied by means of microinjection into the nucleus arcuatus (ARC) and ultraviolet spectrophotometry. The results indicate: (1) The plasma SA level was significantly decreased after microinjection of Glu into the ARC (P < 0.01). With increasing Glu concentration, the onset of the decrease occurred earlier. (2) When Glu was microinjected into ARC after intraventricular injection of apomorphine, the plasma SA level was significantly decreased (P < 0.01) and the time required to cause the decrease was shortened. (3) When Glu was microinjected into ARC after intraventricular injection of spiperone, no change was found in the plasma SA level (P > 0.05). The above results suggest that the mechanism underlying the decrease of plasma SA level is probably related to modulated dopamine (DA) release of hypothalamic dopaminergic neurons by DA-D2 receptor.     

Effects of a microinjection of morphine into the amygdala on the acquisition and expression of conditioned fear and hypoalgesia in rats.

A unilateral microinjection of morphine into the amygdala impaired the acquisition of fear and hypoalgesic responses in rats exposed to a heated floor in a hot-plate apparatus. This impairment was dose dependent, receptor specific, and not observed in rats microinjected with morphine into the caudal basolateral amygdala. A microinjection of morphine into the amygdala reduced the expression of fear responses and of naloxone-sensitive hypoalgesic responses, but did not reduce the expression of naloxone-insensitive hypoalgesic responses. The results document an involvement of opioidergic mechanisms in the amygdala in learned danger and of the amygdala in the control of opioid hypoalgesic responses. They also suggest that learned danger can activate antinociceptive mechanisms independently of the amygdala. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Functional connectivity in the rodent trigeminal pathway grown in vitro

In explant cocultures of the rat trigeminal pathway, embryonic trigeminal ganglion cells grow their axons into peripheral cutaneous and central nervous system targets (R.S. Erzurumlu, S. Jhaveri, Target influences on the morphology of trigeminal axons, Exp. Neurol, 135 (1995) 1-16; R.S. Erzurumlu, S. Jhaveri, H. Takahashi, R.D.G. McKay, Target-derived influences on axon growth modes in explant cocultures of trigeminal neurons, Proc. Natl. Acad. Sci. USA 90 (1993) 7235-7239). In heterochronic cocultures, composed of embryonic trigeminal ganglion, embryonic whisker pad and postnatal brainstem slice, trigeminal axons develop arbors and terminal boutons in the brainstem trigeminal nuclei. To determine whether these terminal arbors establish functional connections with the brainstem neurons, we examined the electrophysiological properties of brainstem neurons and their responsiveness to trigeminal ganglion stimulation. Intracellular recordings were done in vitro on cells of the trigeminal subnucleus interpolaris (SPI) in trigeminal pathway cocultures (E15 whisker pad, E15 trigeminal ganglion, and postnatal day (PND) 0-2 brainstem slice) or in the SPI of acutely prepared brainstem slices. Electrophysiological properties of SPI cells in both preparations were virtually identical. The voltage responses of SPI neurons to intracellular current injection were highly linear suggesting they lacked a number of voltage-dependent conductances. Depolarizing current injection produced trains of action potentials with a frequency that varied with stimulus intensity. In explant cocultures, electrical activation of the trigeminal ganglion evoked EPSPs, and EPSPs coupled with IPSPs in SPI cells. Bicuculline blockade of IPSP activity resulted in long lasting EPSPs whose duration increased with membrane depolarization. These results show that brainstem trigeminal neurons can retain their functional properties in culture and establish functional connections with primary sensory afferents.     

Antinociception produced by microinjection of morphine in the rat periaqueductal gray is enhanced in the foot, but not the tail, by intrathecal injection of alpha1-adrenoceptor antagonists

Antinociception produced by microinjection of morphine in the ventrolateral periaqueductal gray is mediated in part by alpha2-adrenoceptors in the spinal cord dorsal horn. However, several recent reports demonstrate that microinjection of morphine in the ventrolateral periaqueductal gray inhibits nociceptive responses to noxious heating of the tail by activating descending neuronal systems that are different from those that inhibit the nociceptive responses to noxious heating of the feet. More specifically, alpha2-adrenoceptors appear to mediate the antinociception produced by morphine using the tail-flick test, but not that using the foot-withdrawal or hot-plate tests. The present study extended these findings and determined the role of alpha1-adrenoceptors in mediating the antinociceptive effects of morphine microinjected into the ventrolateral periaqueductal gray using both the foot-withdrawal and the tail-flick responses to noxious radiant heating in lightly anesthetized rats. Intrathecal injection of selective antagonists was used to determine whether the antinociceptive effects of morphine were modulated by alpha1-adrenoceptors. Injection of the selective alpha1-adrenoceptor antagonists prazosin or WB4101 potentiated the increase in the foot-withdrawal response latency produced by microinjection of morphine in the ventrolateral periaqueductal gray. In contrast, either prazosin or WB4101 partially reversed the increase in the tail-flick response latency produced by morphine. These results indicate that microinjection of morphine in the ventrolateral periaqueductal gray modulates nociceptive responses to noxious heating of the feet by activating descending neuronal systems that are different from those that inhibit the nociceptive responses to noxious heating of the tail. More specifically, alpha1-adrenoceptors mediate a pro-nociceptive action of morphine using the foot-withdrawal response, but in contrast, alpha1-adrenoceptors appear to mediate part of the antinociceptive effect of morphine determined using the tail-flick test.     

Descending projections from the spinal and mesencephalic nuclei of the trigeminal nerve to the spinal cord in the cat. A study with the horseradish peroxidase technique

Descending projections from the spinal (Vsp) and the mesencephalic nuclei (Vme) of the trigeminal nerve to the spinal cord were studied by means of the retrograde horseradish peroxidase technique in the cat. The number of labeled neurons was largest in the case of high cervical injections and decreased as the injections were placed caudally. Small laminae III and IV neurons of the nucleus caudalis (Vc) were labeled ipsilaterally following injections placed as caudally as the middle cervical segments (C4-C5). Lamina I (marginal) neurons of the Vc were labeled ipsilaterally after injections at the middle thoracic level (T6) but those of C1 were labeled after lumbar injections (L3). Lamina V neurons of C1 and the medullary counterparts were labeled bilaterally after injections placed caudally to thoracic segments. A few small neurons were labeled in the ipsilateral nucleus interpolaris (Vi) after injections placed as caudally as the middle cervical segments (C6). Among the subdivisions of the Vsp, the labeled neurons were most numerous in the nucleus oralis (Vo). They were medium-sized and large, and appeared bilaterally, with an ipsilateral predominance at the level of the superior olive. The great majority projected to the cervical segments but a few also projected to the lower cervical to the thoracic segments (C8-T9). Neurons of the Vme projected ipsilaterally to the upper cervical segments (C1-C3). No projections were found from the principal sensory nucleus. The present study suggests that the trigeminospinal projections of the Vsp and the Vme are composed of various cells of origin and thereby subserve not only the trigeminospinal reflex but other unknown functions.     

Long-latency responses of brain noradrenergic neurons to noxious stimuli are preferentially attenuated by intravenous morphine

The nucleus locus coeruleus (LC) has been strongly implicated in the processing of noxious stimuli. Consistent with this, previous studies have shown that spontaneous LC discharge is depressed by morphine. However, effects of morphine on evoked responses of LC neurons to noxious stimuli have not been systematically examined. We reported recently that responses to footshock stimuli in rat locus coeruleus neurons consist of an early (A-fiber mediated) component and a previously undescribed late (C-fiber mediated) component. In the present study, we administered analgesic doses of morphine (0.1, 0.5, or 1.0 mg/kg, i.v.) to determine the effect on A- and C-fiber components of footshock responses in LC neurons. Doses of 0.5 and 1.0 mg/kg significantly attenuated the C-fiber mediated response of LC neurons without affecting the A-fiber response component. Spontaneous LC discharge was reduced by administration of all doses of morphine. Both depressive effects of morphine were abolished by intravenous administration of naloxone. In contrast, local microinfusion of naloxone into the LC abolished the morphine-induced decrease of spontaneous discharge but did not prevent the depression of the C-fiber mediated footshock response by morphine. This indicates that the site of action for morphine's attenuation of the late LC response to footshock stimulation is outside of the LC. The results are consistent with the hypothesis that the late (C-fiber-mediated) footshock responses in locus coeruleus are involved in the processing of noxious stimuli and may contribute to anti-nociceptive mechanisms.     

Microinjection of thyrotropin-releasing hormone analogue into the central nucleus of the amygdala stimulates gastric contractility in rats

The effect on gastric contractility following bilateral microinjection of thyrotropin-releasing hormone (TRH) analog, RX 77368, into the central nucleus of the amygdala was examined in fasted, urethane-anesthetized rats. Extraluminal force transducers were used to measure gastric corpus contractility. Bilateral microinjection of RX 77368 (0.5 microgram, 1.0 microgram, n = 6 each) stimulated gastric contractility for up to 120 min post-injection, P < 0.05. Gastric contractility was not significantly stimulated by microinjection of 0.1 microgram RX 77368, 0.1% bovine serum albumin (BSA) into the central nucleus or RX 77368 (0.5 microgram, 1.0 microgram) into sites adjacent to the central nucleus. Peak responses (1.0 microgram) occurred 40 min post-injection and represented a 16-26-fold increase over basal values. The frequency of gastric contraction waves was attenuated for 0-90 min in rats receiving central amygdaloid microinjection of RX 77368 (0.1, 0.5 or 1.0 microgram) versus rats microinjected with the vehicle or RX 77368 into sites adjacent to the central nuclei. The stimulatory effect of RX 77368 (1.0 microgram) on gastric contractility was abolished by subdiaphragmatic vagotomy. These results indicate that the TRH analog, RX 77368, acts within the central amygdala to vagally stimulate gastric contractility.     

The mechanism of inhibition of neuronal activity by opiates in the spinal cord of cat

Extra- and intracellular recordings from motoneurones, interneurones and dorsal horn neurones (laminae 4 and 5) were obtained from the lumbar segments (L6-L7) of spinalised (Th 9/10) or pentobarbital-anaesthetised and anaemically decorticated cats. In the majority of spinal neurones microelectrophoretically applied morphine and levorphanol reversibly depressed spontaneous as well as stimulus-evoked and L-glutamate- or acetylcholine-induced activity. There is evidence that opiates block L-glutamate-induced depolarisations by impairing the Na+-influx triggered at the postsynaptic membrane. These depressant effects of opiates could be antagonised by naloxone, and, except in a few cases, were not associated with hyperpolarisation of the cell. Dextrorphan, the D+ enantiomer of levorphanol, displayed no such depressant actions, indicating that stereospecific receptors mediate the depressant effects of opiates. Phoretically applied atropine, procaine and Ca2+ ions have anti-glutamate and anti-acetylcholine actions similar to opiates, but these actions were not antagonised by naloxone. The hyperpolarising effect of glycine was not influenced at dose levels of opiates sufficient to suppress depolarisation induced by L-glutamate or acetylcholine. Microelectrophoretically administered morphine and levorphanol slowed the rate of rise of mono- and polysynaptic EPSPs by a naloxone-antagonisable mechanism at dose levels where almost no alteration in spike shape was detectable. Increased doses of morphine and levorphanol reduced the amplitude of IPSPs and completely blocked or reduced the amplitude of both direct- and antidromically-evoked spikes. These effects of increased doses of opiates were not antagonised by naloxone. Intravenous injection of 2 mg/kg of morphine or 20 mug/kg of Fentanyl mimicked the suppression of spontaneous and evoked neuronal activity observed after phoretic administration. This depressant action of systemically applied opiates could be transiently antagonised by phoretic administration of naloxone. The results are discussed with respect to a stereospecific action of opiates at a postsynaptic receptive site in the spinal cord.     

Muscarine receptor activation in the substantia gelatinosa of the spinal trigeminal nucleus of the guinea pig

1. Intracellular recordings were made from slices of guinea pig spinal trigeminal nucleus pars caudalis (SG). 2. Muscarine [0.3-30 microM; half maximally effective concentration (EC50) = 2.9 microM] hyperpolarized 61% of SG neurons. The effect was mimicked by carbachol (0.3-30 microM; EC50 = 3.9 microM) and antagonized by pirenzepine (1 microM). Thirty-four percent of the neurons were depolarized by muscarine and carbachol (1-30 microM: EC50 = 5.7 microM), and the effect was antagonized by pirenzepine (100 nM). 3. In approximately 80% of recordings, muscarine (10-30 microM) evoked repetitive spontaneous inhibitory postsynaptic potentials (IPSPs) that were sensitive to bicuculline (10 microM). 4. Muscarine (1-30 microM; EC50 = 3 microM) decreased the amplitude of the majority of evoked excitatory postsynaptic potentials (EPSPs), and the effect was mimicked by carbachol and antagonized by pirenzepine (100 nM). 5. These results indicate that there are at least three mechanisms by which muscarine inhibits SG neurons: 1) hyperpolarization through activation of non-M1 receptors; 2) activation of gamma-amino-butyric acid-containing interneurons that mediate IPSPs in a subset of neurons; and 3) a decrease in evoked EPSP amplitude. Muscarine can also activate SG neurons via interaction with an M1-type receptor.     

Strain-dependent morphine-induced analgesic and hyperalgesic effects on thermal nociception in domestic fowl (Gallus gallus).

The effects of morphine (30 mg/kg), naloxone (5 mg/kg), and morphine with naloxone on distress vocalizations and thermal nociception were examined in different strains of domestic fowl. Naloxone by itself did not significantly affect vocalizations or thermal nociception. Morphine produced a naloxone-reversible attenuation of vocalizations that was not strain dependent. Morphine produced a strain-dependent analgesic (Rhode Island Red strain) and hyperalgesic (White Leghorn and Cal-White strains) effect on tests of thermal nociception. Both the analgesic and hyperalgesic effects were reversed by naloxone. These opposite effects on thermal nociception may reflect the effects of selective breeding on opioid receptor subtype. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The differential contribution of spinopetal projections to increases in vocalization and motor reflex thresholds generated by the microinjection of morphine into the periaqueductal gray.

The capacity of morphine microinjected into the ventrolateral periaqueductal gray (vPAG) to elevate the thresholds of spinal motor reflexes (SMRs), vocalizations during shock (VDSs) and vocalization afterdischarges (VADs) was challenged by the intrathecal administration of receptor antagonists to serotonin (methysergide), norepinephrine (phentolamine) and μ-opiates (naloxone). Methysergide and phentolamine were equipotent in reversing increases in SMR thresholds. The efficacy of these antagonists to reduce increases in VDS and VAD thresholds was dependent on the dose of morphine administered into the vPAG. These results indicate that the dose of morphine administered into the vPAG determines the contribution of spinopetal projections in inhibiting dorsal horn neurons involved in reflex generation versus the rostral transmission of pain information. A hypothesis is offered regarding the mechanisms by which vPAG administered morphine suppresses nociceptive transmission through different levels of the neuraxis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

alpha2,3-sialyltransferase mRNA and alpha2,3-linked glycoprotein sialylation are increased in malignant gliomas

Microinjection of a substance P analogue (1 mM; 7 or 10 nl) into laminae I and II of the L7 dorsal horn of decerebrate cats significantly potentiated (P < 0.05) the increase in arterial pressure evoked by microinjection of L-glutamate (109 mM; 7 or 10 nl) into these spinal sites. Microinjection of the substance P analogues (i.e., GR73638 and [Sar9,Met(O2)11]-substance P) which were selective NK-1 receptor agonists, had no impact on the cardioacceleration evoked by microinjection of L-glutamate (P > 0.05). In addition, microinjection of these analogues had no effect on the modest and non-significant increase in phrenic nerve discharge evoked by L-glutamate. We conclude that stimulation of NK-1 receptors in the superficial laminae of the dorsal horn potentiates the pressor responses to microinjection of L-glutamate.     

Chemical stimulation of the intracranial dura induces enhanced responses to facial stimulation in brain stem trigeminal neurons

Chemical activation and sensitization of trigeminal primary afferent neurons innervating the intracranial meninges have been postulated as possible causes of certain headaches. This sensitization, however, cannot explain the extracranial hypersensitivity that often accompanies headache. The goal of this study was to test the hypothesis that chemical activation and sensitization of meningeal sensory neurons can lead to activation and sensitization of central trigeminal neurons that receive convergent input from the dura and skin. This hypothesis was investigated by recording changes in the responsiveness of 23 [16 wide-dynamic range (WDR), 5 high threshold (HT), and 2 low threshold (LT)] dura-sensitive neurons in nucleus caudalis to mechanical stimulation of their dural receptive fields and to mechanical and thermal stimulation of their cutaneous receptive fields after local application of inflammatory mediators or acidic agents to the dura. Responses to brief chemical stimulation were recorded in 70% of the neurons; most were short, lasting the duration of the stimulus only. Twenty minutes after chemical stimulation of the dura, the following changes occurred: 1) 95% of the neurons showed significant increases in sensitivity to mechanical indentation of the dura: their thresholds to dural indentation changed from 1.57 to 0.49 g (means, P < 0.0001), and the response magnitude to identical stimuli increased by two- to fourfold; 2) 80% of the neurons showed significant increases in cutaneous mechanosensitivity: their responses to brush and pressure increased 2.5- (P < 0.05) and 1. 6-fold (P < 0.05), respectively; 3) 75% of the neurons showed a significant increase in cutaneous thermosensitivity: their thresholds to slow heating of the skin changed from 43.7 +/- 0.7 to 40.3 +/- 0.7 degrees C (P < 0.005) and to slow cooling from 23.7 +/- 3.3 to 29.2 +/- 1.8 degrees C (P < 0.05); 4) dural receptive fields expanded within 30 min and cutaneous receptive fields within 2-4 h; and 5) ongoing activity developed in WDR and HT but not in LT neurons. Application of lidocaine to the dura abolished the response to dural stimulation but had minimal effect on the increased responses to cutaneous stimulation (suggesting involvement of a central mechanism in maintaining the sensitized state). Antidromic activation (current of <30 muA) of dura-sensitive neurons revealed projections to the hypothalamus, thalamus, and midbrain. These findings suggest that chemical activation and sensitization of dura-sensitive peripheral nociceptors could lead to enhanced responses in central neurons and that this central sensitization therefore could result in extracranial tenderness (mechanical and thermal allodynia) in the absence of extracranial pathology. The projection targets of these neurons suggest a possible role in mediating the autonomic, endocrine, and affective symptoms that accompany headaches.     

Differential contributions of medullary, thalamic, and amygdaloid serotonin to the antinociceptive action of morphine administered into the periaqueductal gray: A model of morphine analgesia.

The relative contribution of serotonin (5HT) neurotransmission within the medulla (rostral ventromedial medulla) and forebrain (amygdaloid central nucleus and nucleus parafascicularis thalami) to the antinociceptive action of morphine microinjected into the ventrolateral periaqueductal gray (vPAG) was evaluated. The 5HT receptor antagonist methysergide was microinjected into the medulla, forebrain, (or both) after injection of morphine into the vPAG. The contribution of 5HT to the antinociceptive action of morphine was observed to depend on (a) the dose of morphine administered into the vPAG, (b) the site(s) at which methysergide was administered, and (c) the level of the neuraxis at which the behavioral assay was organized. Results of the present study were combined with those of previous studies from this laboratory and presented as a model of the mechanisms by which morphine administered into the vPAG generates its antinociceptive action. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The distribution of afferent neurons in the trigeminal mesencephalic nucleus and the central projection of afferent fibers of the mylohyoid nerve in the rat

Horseradish peroxidase conjugated to wheatgerm agglutinin (HRP:WGA) was injected into the proximal cut ends of three branches of the mylohyoid nerve in rats: the branch to the mylohyoid muscle (BrMh), the branch to the anterior belly of the digastricus muscle (BrDg), and the cutaneous branch (BrCu). HRP-labeled cells were detected in the ipsilateral caudal portion of the trigeminal mesencephalic nucleus (Vmes) and the ipsilateral ventromedial division of the trigeminal motor nucleus, except when HRP:WGA was applied to the BrCu. Morphologically, all labeled Vmes cells were of the pseudounipolar type. Projections of the primary afferents of the BrMh were observed in the ipsilateral trigeminal nucleus caudalis, the upper cervical dorsal horns of laminae I-III, and the dorsolateral recticular formation (Rf), whereas the primary afferents of the BrDg terminated in the ipsilateral trigeminal nucleus principalis and Rf. These observations suggest that the role of the afferent inputs of the mylohyoid muscle differs from that of those of the anterior belly of the digastricus muscle in terms of several functions associated with jaw-closing and infrahyoid muscles.