Non-nociceptive Responses Research Articles

A quantitative comparison of BOLD fMRI responses to noxious and innocuous stimuli in the human spinal cord

Recent studies have shown that functional magnetic resonance imaging (fMRI) can non-invasively assess spinal cord activity. Yet, a quantitative description of nociceptive and non-nociceptive responses in the human spinal cord, compared with random signal fluctuations in resting state data, is still lacking. Here we have investigated the intensity and spatial extent of blood oxygenation level dependent (BOLD) fMRI responses in the cervical spinal cord of healthy volunteers, elicited by stimulation of the hand dorsum (C6–C7 dermatomes). In a block design fMRI paradigm, periods (20 s each) of repetitive noxious (laser heat) or innocuous (brushing) stimulation were alternated with rest. To estimate the level of false positive responses, functional images were acquired during a separate run while subjects were at rest. In a first analysis of averaged peristimulus signals from all voxels within each half of the spinal cord, we found bilateral fMRI responses to both stimuli. These responses were significantly larger during noxious than during innocuous stimulation. No significant fMRI signal change was evident over corresponding time periods during the Rest run. In a second, general linear model analysis, we identified a voxel population preferentially responding to noxious stimulation, which extended rostro-caudally over the length (4 cm) of the explored spinal cord region. By contrast, we found no evidence of voxel populations responding uniquely to innocuous stimuli, or showing decreased activity following either kind of somatosensory stimulus. These results provide the first false-positive-controlled comparison of spinal BOLD fMRI responses to noxious and innocuous stimuli in humans, confirming and extending physiological information obtained in other species.

Transient receptor potential A1 increase glutamate release on brain stem neurons

Low temperature and noxious chemicals activate transient receptor potential (TRP) A1 channel in spinal nociceptive neurons. TRPA1 ligands are found as common ingredients of pungent spices and can trigger autonomic reflexes and alter blood pressure. Recent discovery of TRPA1 on visceral afferent pathway suggests such nonnociceptive responses may be closely related to TRPA1. To understand potential contributions of TRPA1 on autonomic response, we have tested TRPA1 agonist allyl isothiocyanate (AITC) effects on mechanically dispersed nucleus tractus solitarii neurons. AITC of 200 microM increased glutamate release in 58% of tested neurons and TRP channel antagonist ruthenium red (50 microM) blocked the AITC actions. tetrodotoxin and Cd did not eliminate AITC-evoked glutamate release increase. TRPA1 expressed in capsaicin-sensitive and insensitive neurons.

Nociceptive spinothalamic tract and postsynaptic dorsal column neurons are modulated by paraventricular hypothalamic activation

Previously, we demonstrated that stimulation of the paraventricular hypothalamic nucleus diminishes the nociceptive dorsal horn neuronal responses, and this decrease was mediated by oxytocin in the rat. In addition, we have proposed that oxytocin indirectly inhibits sensory transmission in dorsal horn neurons by exciting spinal inhibitory GABAergic interneurons. The main purpose of the present study was to identify which of the neurons projecting to supraspinal structures to transmit somatic information are modulated by the hypothalamic-spinal descending activation. In anaesthetized rats, single-unit extracellular and juxtacellular recordings were made from dorsal horn lumbar segments, which receive afferent input from the toe and hind-paw regions. The projecting spinothalamic tract and postsynaptic dorsal column system were identified antidromically. Additionally, in order to label the projecting dorsal horn neurons, we injected fluorescent retrograde neuronal tracers into the ipsilateral gracilis nucleus and contralateral ventroposterolateral thalamic nucleus. Hence, juxtacellular recordings were made to iontophoretically label the recorded neurons with a fluorescent dye and identify the recorded projecting cells. We found that only nociceptive evoked responses in spinothalamic tract and postsynaptic dorsal column neurons were significantly inhibited (48.1 +/- 4.6 and 47.7 +/- 8.2%, respectively) and non-nociceptive responses were not affected by paraventricular hypothalamic nucleus stimulation. We conclude that the hypothalamic-spinal system selectively affects the transmission of nociceptive information of projecting spinal cord cells.

Control of Chronic Pain by the Ubiquitin–Proteasome System in the Spinal Cord

Chronic pain is maintained in part by long-lasting neuroplastic changes in synapses and several proteins critical for synaptic plasticity are degraded by the ubiquitin-proteasome system (UPS). Here, we show that proteasome inhibitors administered intrathecally or subcutaneously prevented the development and reversed nerve injury-induced pain behavior. They also blocked pathological pain induced by sustained administration of morphine or spinal injection of dynorphin A, an endogenous mediator of chronic pain. Proteasome inhibitors blocked mechanical allodynia and thermal hyperalgesia in all three pain models although they did not modify responses to mechanical stimuli, but partially inhibited responses to thermal stimuli in control rats. In the spinal cord, these compounds abolished the enhanced capsaicin-evoked calcitonin gene-related peptide (CGRP) release and dynorphin A upregulation, both elicited by nerve injury. Model experiments demonstrated that the inhibitors may act directly on dynorphin-producing cells, blocking dynorphin secretion. Thus, the effects of proteasome inhibitors on chronic pain were apparently mediated through several cellular mechanisms indispensable for chronic pain, including those of dynorphin A release and postsynaptic actions, and of CGRP secretion. Levels of several UPS proteins were reduced in animals with neuropathic pain, suggesting that UPS downregulation, like effects of proteasome inhibitors, counteracts the development of chronic pain. The inhibitors did not produce marked or disabling motor disturbances at doses that were used to modify chronic pain. These results suggest that the UPS is a critical intracellular regulator of pathological pain, and that UPS-mediated protein degradation is required for maintenance of chronic pain and nociceptive, but not non-nociceptive responses in normal animals.

A Role of the Ubiquitin–Proteasome System in Neuropathic Pain

Neuropathic pain (characterized by hyperalgesia and allodynia to mechanical and thermal stimuli) causes cellular changes in spinal dorsal horn neurons, some of which parallel those in synaptic plasticity associated with learning. Ubiquitin C-terminal hydrolase (UCH) appears to play a key role in long-term facilitation in Aplysia. The cooperation of UCH with the proteolytic enzyme complex known as the proteasome is required for the degradation of a number of signaling molecules within the cell that may remove normal restraints on synaptic plasticity. We have used electrophysiology, in situ hybridization histochemistry, semiquantitative RT-PCR, Western blotting, and in vivo behavioral reflex analysis to investigate the ubiquitin-proteasome system in a model of neuropathic pain. In neuropathic animals, ionophoretic application of selective proteasome inhibitors attenuated dorsal horn neuron firing evoked by normally innocuous brush or cold stimuli and by noxious mustard oil stimuli. In control animals, only mustard oil-evoked responses were inhibited. Intrathecal administration of proteasome inhibitors attenuated hyperalgesia and allodynia in neuropathic rats. Expression of UCH-L1 (a rat homolog of Aplysia neuronal UCH and of the human UCH-L1, also known as PGP 9.5) and its mRNA were selectively increased within the ipsilateral dorsal horn of neuropathic rats, supporting the idea of a role for the ubiquitin-proteasome system in nociceptive processing. Proteasome inhibitors selectively attenuate allodynic and hyperalgesic responses in neuropathic pain, with some reduction in normal nociceptive, but not non-nociceptive responses, and potentially represent a novel therapeutic strategy for neuropathic pain.

Inescapable shock-induced potentiation of morphine analgesia.

Exposure to various stressors potentiates nociceptive and nonnociceptive responses to morphine. These phenomena have received little study despite their seeming generality and importance for understanding analgesia and opiate action. The present experiments characterize inescapable shock (IS)-induced potentiation of morphine analgesia. Rats were exposed to IS, equal escapable shocks (ESs), or restraint (control). Potentiation of analgesia (tail-flick [TF] test and hotplate test) was observed only in rats given IS 24 or 48 hr earlier, in agreement with previously reported learned-helplessness effects. Finally, no change in tail temperature or motor function was found that could be inaccurately interpreted as analgesia. The relevance of these findings to stressor-induced enhancement of morphine analgesia and potential substrates of IS effects are discussed.

Studies of synaptic transmission in vivo: indirect versus direct effects of ( RS)-α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid/kainate antagonists on rat spinal sensory responses

The ( RS)-α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)/kainate receptor antagonists 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo [ƒ]quinoxaline (NBQX) and 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) were examined by microiontophoretic administration in electrophysiological tests on spinal neurones in α-chloralose anaesthetized rats. The antagonists significantly reduced extracellularly recorded nociceptive and non-nociceptive responses, as expected; concurrently they reduced background discharge. When the background discharge rate was held constant, the antagonists no longer significantly reduced the evoked responses. This indicates that in the absence of such control, the antagonists decreased cell excitability and only indirectly affected the test responses. Unless such indirect effects have been controlled for, the interpretation of the actions of AMPA/kainate antagonists on evoked synaptic responses is compromised and may be erroneous.

Exposure of rat spinal neurones to NMDA, AMPA and kainate produces only short-term enhancements of responses to noxious and non-noxious stimuli

The ability of excitatory amino acids (EAAs) to modulate nociceptive and non-nociceptive responses was tested on spinal neurones of the anaesthetized rat. NMDA ( N- methyl- d-aspartate ), AMPA ((RS)-α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate) and kainate were applied by iontophoretic ejection to increase the background firing rate of each cell to ∼25 spikes/s. Responses to noxious heat and pinch and innocuous tap stimuli were enhanced to similar degrees by all three EAAs and returned to control immediately following termination of EAA ejection. This result shows that, whilst NMDA does enhance synaptic responses of spinal neurones, this effect is little or no greater than for AMPA or kainate. Furthermore, the rapid recovery of nociceptive responses indicates that more than NMDA receptor activation alone is required to induce longer-term enhancement of nociceptive responses (hyperalgesia).

Parabrachial area and nucleus raphe magnus-induced modulation of nociceptive and nonnociceptive trigeminal subnucleus caudalis neurons activated by cutaneous or deep inputs.

1. The aim of this study was to test whether parabrachial area (PBA) stimulation exerts inhibitory influences on the spontaneous activity and responses evoked by skin and deep afferent inputs in trigeminal subnucleus caudalis (Vc) neurons, and to compare these effects with those of nucleus raphe magnus (NRM) stimulation. A total of 92 nonnociceptive and nociceptive Vc neurons was recorded in urethan/alpha-chloralose-anesthetized rats. Each neuron was functionally classified as low-threshold mechanoceptive (LTM), wide dynamic range (WDR), nociceptive-specific (NS), nociceptive convergent with both skin and deep inputs (S+D), or deep nociceptive (D); the LTM neurons could be subdivided as rapidly adapting (RA) or slowly adapting (SA). Conditioning stimulation was applied to histologically verified sites in PBA and NRM. 2. The spontaneous or evoked activity of all classes of neurons could be inhibited by PBA as well as by NRM stimulation, but generally the incidence and magnitude of inhibition were lower for the LTM neurons. Occasionally, facilitation of neuronal activity was also produced by PBA and NRM stimulation. 3. The spontaneous activity of 11 LTM neurons (6 RA, 5 SA), 13 nociceptive neurons (6 WDR, 7 NS), and 5 D neurons was tested with stimulation of PBA or NRM or both. LTM spontaneous activity was more significantly inhibited by NRM stimulation than by PBA stimulation, whereas both NRM and PBA stimulation had similar and significant inhibitory effects on NS, WDR, and D neurons. 4. The evoked nonnociceptive responses of 28 LTM neurons (16 RA, 12 SA) and of 6 WDR neurons were also tested with stimulation of PBA or NRM or both. The magnitudes of inhibition of the responses produced by PBA conditioning stimulation were statistically significantly less than those induced by NRM conditioning stimulation. 5. The cutaneous and deep nociceptive responses of cutaneous nociceptive neurons (9 NS, 19 WDR) and seven D neurons, respectively, were also tested with PBA and NRM stimulation. There was a significant difference in potency between PBA- and NRM-induced inhibition, but no difference in the magnitude of inhibitory effects among NS, WDR, and D neurons. For both PBA and NRM conditioning stimulation, graded increases in intensities of stimulation produced linear increases in inhibitory effects on nociceptive responses; an increase in stimulation frequency from 5 to 400 Hz also produced increases in inhibition of the nociceptive responses. 6. In five S+D nociceptive convergent neurons, the responses elicited by deep inputs were more powerfully inhibited by PBA stimulation than those elicited by cutaneous inputs.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of herpes simplex virus type-1 inoculated in the hind paw on the nociceptive and nonnociceptive behavioral responses of the rat

Effects of herpes simplex virus type-1 inoculated in the hind paw on the nociceptive and nonnociceptive behavioral responses of the rat

Effects of excitatory amino acid receptor antagonists on a capsaicin-evoked nociceptive reflex: a comparison with morphine, clonidine and baclofen

The rat isolated spinal cord-tail preparation has been employed to examine the effects of several antinociceptive drugs and excitatory amino acid (EAA) receptor antagonists on nociceptive reflexes (recorded in ventral roots) stimulated by peripheral application of capsaicin (CAP). Non-nociceptive monosynaptic and polysynaptic dorsal root-evoked ventral root potentials (DR-VRPs) were also examined. Morphine (0.01–3 μM) and clonidine (0.03–1 μM) inhibited CAP-stimulated activity, but not the non-nociceptive dorsal root-evoked monosynaptic reflex (MSR) or polysynaptic (PSR) activity. These effects were antagonized by naloxone and efaroxan, respectively. The AMPA/KA receptor antagonists CNQX (0.1–100 μM) and DNQX (0.1–30 μM) blocked nociceptive activity and were 4-fold selective for CAP-evoked potentials compared to the monosynaptic reflex. Kynurenate (1–300 μM), dl-AP-4 (3–300 μM), l-AP-4 (3–300μM), and the GABA B receptor agonist baclofen (0.1–10 μM), inhibited all evoked potentials with relatively little selectivity between nociceptive and non-nociceptive responses. NMDA receptor antagonism by AP-5 (100 μM) reduced nociceptive and non-nociceptive potentials by a maximum of 30–33%. These data indicate that AMPA/KA receptor-mediated synapses are involved in acute spinal nociceptive transmission and suggest that AMPA/KA receptor subtypes could provide novel analgesic targets.

Effects of intravenous mu and kappa opioid receptor agonists on sensory responses of convergent neurones in the dorsal horn of spinalized rats.

1. Electrophysiological experiments have been performed to assess the effects of intravenously administered mu and kappa opioid agonists on the responses to noxious thermal and mechanical and non-noxious tactile stimuli of single convergent neurones in laminae III-VI of the dorsal horn of spinalized rats anaesthetized with alpha-chloralose. 2. The mu receptor agonists tested were fentanyl (1-16 micrograms kg-1) and morphine (0.5-16 mg kg-1) and the kappa-receptor agonists U-50,488 (1-16 mg kg-1) and tifluadom (0.1-1.6 mg kg-1). Multiple drug tests were made on each cell so that compounds could be compared under closely comparable conditions. 3. In one protocol, thermal and mechanical nociceptive responses of matched amplitudes were elicited alternately. Both mu and kappa agonists dose-dependently reduce the neuronal responses. Thermal nociceptive responses were as sensitive to the kappa agents as were the mechanical nociceptive responses; the mu agonists similarly reduced both types of response in parallel. 4. In another protocol, nociceptive and non-nociceptive responses were elicited alternately to permit the degree of selective antinociception to be assessed. The mu agonists were scarcely selective, fentanyl reducing nociceptive only slightly (but significantly at 4-16 micrograms kg-1) more than non-nociceptive responses. The kappa-opioid agonist U50,488 reduced tactile responses somewhat more than nociceptive responses. 5. The spontaneous discharge of these cells with ongoing activity was reduced to a significantly greater degree than the evoked responses; this is likely to have contributed to the non-selectivity of the reduction of the evoked responses. 6. The results are discussed with respect firstly to previous reports that K opioids are ineffective in tests of thermal nociception, and secondly to the likely spinal mechanisms by which opioid receptor agonists mediate antinociception.

The involvement of neurokinin receptor subtypes in somatosensory processing in the superficial dorsal horn of the cat

As well as substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) have recently been found in the superficial dorsal horn of the spinal cord; NKA originating mainly in fine primary afferents. We have investigated the effects of these tachykinins and a range of analogues on somatosensory responses of single identified dorsal horn neurons, when applied ionophoretically to the region of the substantia gelatinosa. Behavioural reflex tests of thermal nociception were carried out in parallel. The role of NK-1, NK-2 and NK-3 receptors was addressed. NK-1-selective agonists attenuated the non-nociceptive responses of identified multireceptive spinocervical tract (SCT) neurons. Of the endogenous tachykinins, both SP and NKB (a weak NK-1 agonist) showed this effect. No role for NK-3 receptors was identified in our experiments. NK-2-selective agonists (including NKA) caused a unique and selective facilitation of thermal nociceptive responses. NKA also reduced reflex response latency in tail-flick and hot plate tests. NKA as a primary afferent transmitter may thus be involved in mediating or facilitating the expression of thermal nociceptive inputs in the substantia gelatinosa. NKA and SP could be considered as acting in concert in the superficial dorsal horn in an effectively pro-nociceptive modulatory role. Evidence from receptor-selective antagonists supports that obtained with agonists for the roles of particular NK receptors in somatosensory processing. NK-2, but not NK-1 or NK-3 antagonists attenuated endogenous thermal nociceptive responses, supporting the hypothesis that an NK-2 agonist (such as NKA) may normally participate in expression of thermal nociception in the superficial dorsal horn. Behavioural experiments showing increased response latencies with a putative NK-2 selective antagonist further supported the involvement of NK-2 receptors in thermal nociception.

Effect of electroacupuncture of neuronal responses of the cat oral trigeminal nucleus during nociceptive and non-nociceptive stimulation

UDC 615.844.4.015.4:612.822].076.9 Interest in the oral trigeminal nucleus (OTN) in connection with the study of pain has increased considerably after the discovery of a well-marked focus of evoked activity in it during nociceptive stimulation of the orofacial receptive fields. The so-called dual representation of pain in the trigeminal complex [2] called for a close study of all features of the organization of the various nuclei of this concept (the oral, in particular), which could be responsible for their specific role in the conduction of nociceptive and non-nociceptive signals in the CNS. Despite several investigations of the organization of the afferent input and neuronal responses of OTN, only a few investigators [4] have attempted to study this problem from the standpoint of discovery of different functional types of neurons, involved in the conduction of nociceptive and non-nociceptive signals, as has been done in relation to the caudal trigeminal nucleus [8]. From this point of view it is interesting to study the character of the effect of electroacupuncture (EAP), an effective modulator of nociceptive signals. The aim of this investigation was to study the effect of EAP on responses of neurons of different functional types in OTN to noceptive and non-nociceptive stimulation. EXPERIMENTAL METHOD Acute experiments were carried out on eight adult cats weighing 2.5-4 kg. The dissection was carried out under hexobarbital anesthesia (15 mg/kg, intraperitoneall y), and the animals were subsequently immobilized with suxamethonium and artificially ventilated. Unit activity was recorded extracellularly by glass microelecrodes with a tip 1-3 ~ in diameter, filled with 2 M KCI solution, and with a resistance of 4-10 M~, with the aid of a YC-10 electrophysiological complex ("Nihon Kohden," Japan). Pulsation of the brain was prevented by flooding its surface with agar-agar. Stimulation of the dental pulp and of the lip with square pulses, i and 0.i msec respectively in duration and with a strength of 0-50 mA, by means of an ESU-2 stimulator was used as testing stimulation. The nociceptive character of afferent stimulation of a particular intensity was determined by preliminary study of the thresholds of onset of non-nociceptive and nociceptive behavioral responses of the animals to both types of stimulation. Depending on the character of their response to electrical stimulation of the dental pulp and lip, the neurons were divided into three groups. Neurons of group i responded to weak stimulation and their response was unchanged when the strength of stimulation was increased. They were regarded as non-nociceptive low-threshold neurons (LT neurons). Neurons of the second group also began to respond to weak stimulation of lip or dental pulp, but the neuron discharged more strongly when its intensity was increased. Such neurons were classed as neurons with wide dynamic range (WDR neurons). Finally, neurons of the third group responded only to intensive stimulation of the dental pulp and lip, and they were accordingly characterized as specific nociceptors (SN neurons). EAP was applied through steel needles, inserted into the lower part of the base of the concha auriculae. The duration of the pulses was 1.2 msec, their frequency i Hz, their intensity about I0 mA, and stimulation lasted for 5-i0 rain. Research Institute of Reflex Therapy, Moscow. (Presented by Academician of the Academy

Nociceptive flexion reflexes during analgesic neurostimulation in man

Nociceptive flexion reflexes of the lower limbs (RIII responses) have been studied in 21 patients undergoing either epidural (DCS, n = 16) or transcutaneous (TENS, n = 5) analgesic neurostimulation (AN) for chronic intractable pain. Flexion reflex RIII was depressed or suppressed by AN in 11 patients (52.4%), while no modification was observed in 9 cases and a paradoxical increase during AN was evidenced in 1 case. In all but 2 patients, RIII changes were rapidly reversible after AN interruption. RIII depression was significantly associated with subjective pain relief, as assessed by conventional self-rating; moreover, in 2 patients it was possible to ameliorate the pain-suppressing effects of AN by selecting those stimulation parameters (intensity and frequency) that maximally depressed nociceptive reflex RIII. We recorded 2 cases of RIII attenuation after contralateral neurostimulation. AN appeared to affect nociceptive reflexes rather selectively, with no or very little effect on other cutaneous, non-nociceptive responses. Recording of RIII reflexes is relatively simple to implement as a routine paraclinical procedure. It facilitates the objective assessment of AN efficacy and may help to choose the most appropriate parameters of neurostimulation. In addition, RIII behavior in patients could be relevant to the understanding of some of the mechanisms involved in AN-induced pain relief.

Idazoxan blocks the action of noradrenaline but not spinal inhibition from electrical stimulation of the locus coeruleus and nucleus Kolliker-Fuse of the cat

The effects of idazoxan, a specificα 2-adrenoceptor antagonist, on spinal inhibition by administration of noradrenaline and from electrical stimulation of the dorsolateral pons were studied in 26 cats anaesthetized with sodium pentobarbitone. The excitation of dorsal horn neurons of the spinal cord by noxious heating of the skin or by impulses in unmyelinated primary afferent fibres was markedly reduced when noradrenaline was administered microelectrophoretically in the substantia gelatinosa or near cell bodies. Electrical stimulation of the region of the locus coeruleus selectively inhibited spinal nociceptive transmission when dorsal horn neurons were excited by noxious and non-noxious stimuli. In contrast to stimulation of the locus coeruleus, stimulation of the nucleus Kolliker-Fuse produced non-selective inhibition of both nociceptive and non-nociceptive responses of dorsal horn neurons of the spinal cord. Microelectrophoretic ejection of idazoxan reduced or abolished noradrenaline-induced inhibition with 19 of 20 neurons. This antagonist did not alter inhibition from stimulation of the locus coeruleus and the nucleus Kolliker-Fuse, regardless of whether it was administered microelectrophoretically (11 neurons), systemically (3 neurons) or topically (4 neurons). The results suggest thatα 2-adrenoceptors do not mediate inhibiton of spinal nociceptive transmission from electrical stimulation of the locus coeruleus and the nucleus Kolliker-Fuse. Other possibilities for the failure of idazoxan to modify inhibition from such stimulation are discussed.

Lack of interaction between methionine enkephalin and d-phenylalanine on nociceptive and non-nociceptive responses of dorsal horn neurones of the cat

In the spinal cord of the barbiturate anaesthetized cat, D-phenylalanine (DPA) depressed spontaneous and amino acid-induced firing of multireceptive dorsal horn neurones. The excitation of these neurons by noxious and non-noxious cutaneous stimuli was non-selectively depressed by DPA. DPA did not potentiate the depressant action of methionine enkephalin on these cells. Although naloxone reduced the depressant action of DPA, this was associated with increases in spontaneous firing. Spinal reflexes in this preparation are tonically inhibited by opioid peptides. Intravenous DPA (20–70 mg/kg) did not potentiate this inhibition but produced small increases in spinal reflexes. Collectively these data do not support the hypothesis that analgesia from DPA results from potentiation of endogenously released methionine enkephalin.

Nociceptive and non-nociceptive responses of neurons in the medial subthalamic region and lateral hypothalamic area of cats and their relationship to the effects of morphine and pentazocine.

Single neuronal activity was recorded extracellularly from the Forel's field (FH), subthalamic region immediately rostral to the FH (STRF), rostral end of the medial subthalamic region (RE) and lateral hypothalamic area (LHA) of the anesthetized cats. Many of the FH, RE and LHA neurons were excited by nociceptive stimulation such as pinching the skin with serrated forceps and/or intra-arterial injection of bradykinin. These nociceptive neurons were also excited by non-nociceptive stimulation such as tap of deep tissues, bending hairs with an air-puff and/or joint rotation. On the other hand, inhibition by both nociceptive and non-nociceptive stimuli was seen in and around the rostral end of the FH including STRF. Their receptive fields were large. After intravenous administration of either morphine or pentazocine, most nociceptive neurons became unresponsive to nociceptive stimuli, although they were driven by non-nociceptive stimuli. This suggests that morphine and pentazocine have a specific antinociceptive action on these nociceptive neurons. Intravenous naloxone reversed the antinociceptive action of morphine, but failed to reduce the action of pentazocine. This differentiation has an important functional significance.

Raphe and periaqueductal gray induced suppression of non-nociceptive neuronal responses in the dorsal column nuclei and trigeminal subnucleus caudalis

Raphe and periaqueductal gray induced suppression of non-nociceptive neuronal responses in the dorsal column nuclei and trigeminal subnucleus caudalis

Inhibition of nociceptive and nonnociceptive responses of primate spinothalamic cells by stimulation in medial brain stem.

Inhibition of nociceptive and nonnociceptive responses of primate spinothalamic cells by stimulation in medial brain stem.