Nociceptive Behavior In Rats Research Articles

The peripheral role of group I metabotropic glutamate receptors on nociceptive behaviors in rats with knee joint inflammation

We examined whether the mGluR1 and mGluR5 were involved in development and maintenance of behavioral signs of non-evoked pain and secondary mechanical hyperalgesia induced by knee joint inflammation. Selective mGluR1 antagonist, (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA: 50, 100, 200 μM/25 μl, n = 10 per group) and selective mGluR5 antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP: 50, 100, 200 nM/25 μl, n = 10 per group) was intra-articularly (i.a.) injected 30 min before and 4 h after carrageenan injection and behavioral tests were conducted. In the pre-treatment, only a higher dose (200 nM) of MPEP significantly prevented the magnitude of weight load reduction, whereas AIDA (200 μM) and MEPE (50, 100 and 200 nM) significantly reduced the development of mechanical hyperalgesia compared to saline treated group. In the post-treatment, AIDA (200 μM) and MPEP at 100 and 200 nM partially reversed the reduction of weight load induced by carrageenan. MPEP significantly increased the withdrawal threshold to mechanical stimulation in a dose-dependent manner, whereas AIDA had significantly reversed the decreased the paw withdrawal threshold only at 200 μM. The present study demonstrated that i.a. MPEP, selective mGluR5 antagonist is more effective than selective mGluR1 antagonist, AIDA on non-evoked pain as well as mechanical hyperalgesia in both induction and maintenance phase in knee joint inflammation. It is suggested that peripheral mGlu5 receptors play a more prominent role in inflammatory pain including evoked and spontaneous pain. Thus, selective mGluR5 antagonist could be effective therapeutic tools in clinical setting.

Effects of neonatal testosterone treatment on sex differences in formalin-induced nociceptive behavior in rats

Effects of neonatal testosterone treatment on sex differences in formalin-induced nociceptive behavior in rats

Effects of neonatal testosterone treatment on sex differences in formalin-induced nociceptive behavior in rats

There are sex differences in nociceptive behavior induced by formalin in rats. To determine whether these sex differences are the result of the sexual differentiation of the brain, that is masculinization and defeminization [A.P. Arnold, R.A. Gorski, Gonadal steroid induction of structural sex differences in the central nervous system, Annu. Rev. Neurosci. 7 (1984) 413–442; M.M. McCarthy, A.T.M. Konkle, When is a sex difference not a sex difference? Front Neuroendocrinol. 26 (2005) 85–102], some female rats were injected with testosterone propionate (TP, 100 μg/25 μl/rat) on the day of birth and on the following day. As controls, other female rats and all male rats were injected with the same volume of sesame oil. They were castrated at the age of 8 weeks, and implanted with a silicon tube containing 20% of 17β-estradiol or cholesterol. Two weeks after the implantation, rats were injected with 50 μl of 2% formalin in the right hind paw and their behavioral changes were observed for 1 h. In cholesterol-implanted rats, all rats exhibited three typical phases of pain response and there were no significant differences in the scores of nociceptive behavior. In 17β-estradiol implanted rats, female and TP-treated female rats had a significantly higher score of nociceptive behavior than male rats. These results indicate that estrogen produces sex differences in nociceptive behavior induced by formalin, and suggest that these differences are not due to the sexual differentiation of the brain, since the dose and the timing of the TP treatment effectively defeminize and masculinize female rats. Alternatively, sexual differentiation of the brain response to formalin-induced nociceptive behavior may be different from ordinary sexual differentiation.

Antinociceptive effect of intra-hippocampal CA1 and dentate gyrus injection of MK801 and AP5 in the formalin test in adult male rats

Previous research has shown that the hippocampus processes pain related-information, probably through hippocampal neurons that respond exclusively to painful stimulation. In the current experiments we tested whether blocking NMDA receptors in the hippocampal CA1 region and dentate gyrus could reduce nociceptive behaviors in rats. The competitive and noncompetitive NMDA receptor antagonists 2-amino-5-phosphonopentanoic acid (AP5; 3.75 μg/0.75 μl) and MK801 (1.5, 3, 6 μg/0.5 μl) were injected into the dentate gyrus and CA1 area of behaving rats 5 min before subcutaneous injection of formalin irritant. Pain behaviors in both acute and tonic phases of the formalin test were significantly reduced by AP5 (3.75 μg/0.75 μl) and MK801 (3 μg/0.5 μl, but not 1.5 and 6 μg/0.5 μl) injection to the dentate gyrus. In the CA1, injection of AP5 had no effect while injection of the effective dose of MK801 (3 μg/0.5 μl) had a significant antinociceptive effect. This effect was apparent only during the late phase of the formalin test. These results support the hypothesis that NMDA-sensitive mechanisms are involved in acute and persistent pain-related processing in the dentate gyrus and with tonic pain processing in the hippocampal CA1 region.

Downregulation of Cytosolic Prostaglandin E2Synthase Results in Decreased Nociceptive Behavior in Rats

Nociception-evoked prostaglandin E2 (PGE2) release in the spinal cord contributes considerably to the development of hyperalgesia and allodynia. Biosynthesis of PGE2 involves the conversion of arachidonic acid to PGH2 by cyclooxygenases (COXs), followed by an isomerization of PGH2 to PGE2 by PGE2 synthases (PGESs). The roles of COX-1, COX-2, and the inducible microsomal PGES-1 have been studied in models of pain and inflammation. In contrast, in nociceptive processes, very little is known about the role of cytosolic PGES (cPGES), which has been described as being functionally coupled to COX-1. Here we show by in situ hybridization and immunohistological analysis that COX-1 and cPGES are constitutively expressed in neuronal and non-neuronal cells of the dorsal and ventral horns in the spinal cord of adult rats. The protein levels of both enzymes were not regulated by nociceptive stimuli; however, reduction of cPGES in rat spinal cord with intrathecal application of cPGES antisense oligonucleotides reduced the nociceptive behavior in zymosan-evoked thermal hyperalgesia and in the formalin assay. The data indicate that cPGES plays an important role in mediating early responses during spinal nociceptive processing.

Endogenous and exogenous melanocortin antagonists induce anti-allodynic effects in a model of rat neuropathic pain

A number of studies suggest melanocortin (MC) system involvement in nociceptive modulation. Although the mechanism through which this occurs is still unknown, experimental evidence would suggest a primary role of MC4 receptors. To further investigate the implication of this MC receptor subtype in chronic pain, we have studied the effects of several MC antagonists on spinal nerve ligation-induced nociceptive behavior in rats. The intrathecal injection of synthetic antagonists with different selectivity to MC4 receptor and of an endogenous antagonist (Agouti related protein; AgRP) reduced mechanical allodynia in neuropathic rats, as measured by von Frey hair test. Treatments produced an anti-allodynic effect at the dose of 1.5 nmol (25–30% maximum possible effect, MPE, P < 0.05). To further investigate the possible physiological role of AgRP in pain modulation we studied its expression in both sham and neuropathic rat spinal cord and dorsal root ganglia (DRG) by quantitative real time PCR and immunohistochemistry. AgRP was present in both spinal cord and DRG, and its expression, was unchanged in neuropathic animals. In conclusion MC4 receptor antagonists with different selectivity profile, induce anti-allodynic effects in one of the most relevant neuropathic pain model. In addition the expression of AgRP in spinal cord and DRG suggests an endogenous tonic inhibitory control on MC system activity. In pathological conditions this steady control could be insufficient to cope with an over activated MC system leading to increase in nociception. These data suggest that targeting MC4 with synthetic antagonists could restore the balance and hence reduce nociception.

Attenuation of nociception in a model of acute pancreatitis by an NK-1 antagonist

Substance P (SP) acting at the NK-1 neurokinin receptor has a well-documented role in the transmission and maintenance of nociceptive information. SP is found in the majority of fibers innervating the pancreas, and it is up-regulated after pancreatic inflammation. The aim of this study was to investigate the role of the NK-1 receptors in the maintenance of pancreatic nociception. Using a newly developed rat model of acute pancreatic nociception that persists for 1 week, the NK-1 receptor expression in the spinal cord and pancreas was examined using immunohistochemistry and Western blotting procedures. The effects of a specific NK-1 antagonist, CP99,994, on the behavioral manifestations of pancreatic nociception were determined. The antagonist was administered intraperitoneally and intrathecally to differentiate peripheral and central effects. Injection of CP-100,263, the inactive enantiomer of CP-99,994 was used as a control for nonspecific effects of the antagonist. Immunohistochemistry and Western blotting analysis revealed an up-regulation of the NK-1 receptor occurs in the pancreas but not at the spinal cord level. The NK-1 antagonist was able to attenuate the nociceptive behaviors in rats with pancreatitis when applied intraperitoneally with a short duration of effectiveness. Intrathecal application of the antagonist was ineffective. These results suggest the involvement of pancreatic NK-1 receptors in the maintenance of nociception during pancreatic inflammation.

Effects of gender and gonadal hormones on nociceptive responses to intraplantar carrageenan in the rat

The effects of gender and gonadal hormones on nociceptive responses to intraplantar carrageenan in the rat were investigated. A plantar analgesic meter was used to measure carrageenan-induced changes in paw withdrawal latency (PWL) values, and von Frey monofilaments were used to assess changes in paw withdrawal threshold (PWT) values in response to tactile-evoked (mechanical) stimuli. The data revealed that PWL values were significantly greater in gonadally-intact females than in gonadally-intact males, and this response was abolished by surgical gonadectomies. Gonadally-intact as well as gonadectomized male and female rats also exhibited significant carrageenan-induced decreases in PWT, but neither sex- nor gonadectomy-related differences were detected in the development of mechanical allodynia. These findings demonstrate that intraplantar carrageenan induces nociceptive behaviors in rats that are differentially affected by sex and gonadal hormones.

Spinal nociceptin inhibits septide but not N-methyl- d-aspartate-induced nociceptive behavior in rats

Nociceptin can induce spinal analgesia in rats. Here, we tested the ability of nociceptin to inhibit the nociceptive behavior (biting, scratching, licking) induced by intrathecal administration of N-methyl- d-aspartate (4 μg) or the tachykinin NK 1 receptor agonist, septide (0.5 μg), in rats. Intrathecal nociceptin (3–30 nmol) did not modify the NMDA-induced behavior. However, coadministration of nociceptin (1–10 nmol) inhibited the septide-induced excitatory response. This inhibition was unaffected by systemic (10 mg/kg) or intrathecal (30 nmol) administration of naloxone, but intrathecal coadministration of the ORL1 (opioid receptor-like type 1) receptor antagonist [Nphe 1]nociceptin-(1-13)-NH 2 (30–90 nmol) prevented it, suggesting the involvement of ORL1 receptors.

Nociceptive behaviour of rats exposed to 50 Hz moderate intensity Electric Field during development

There is mounting evidence about the interaction of extremely low frequency electromagnetic fields (EMF) with the bio-system. The present investigation was aimed to explore the effect of EMF on nociceptive behaviour in rats. Nociceptive behaviour to phasic noxious stimuli and its emotional component were compared in rats exposed to EMF for 30 or 54 days. The results suggest that only the emotional component of the phasic pain was affected by the applied field.

Systemic ketamine attenuates nociceptive behaviors in a rat model of peripheral neuropathy

The efficacy of ketamine (KET), a non-competitive NMDA receptor-channel blocker, was assessed in relieving nociceptive behaviors in neuropathic rats with tight ligations of the L5 and L6 spinal nerves. The antinociceptive effects of KET were dose- and time-dependent. A systemic injection of 0.01 mg/kg KET transiently (15–30 min) attenuated several nociceptive behaviors, including mechanical allodynia and hyperalgesia, cold allodynia, spontaneous pain, and cold stress-induced pain. Treatment with 1.0 mg/kg KET consistently decreased all nociceptive behaviors for 45–75 min, without noticeable side effects. Higher doses (25 and 50 mg/kg) provided longer lasting relief; however, these doses resulted in transient motor impairment which lasted for 15–30 min post-injection. Systemic KET was most effective in decreasing the behavioral signs of mechanical allodynia and hyperalgesia, followed by cold allodynia, cold stress-induced pain, and spontaneous pain. The present results demonstrate that blockade of NMDA receptors effectively alleviates nociceptive behaviors in a rat model of peripheral neuropathy, substantiating the important role of these receptors in the central sensitization that underlies the maintenance of neuropathic pain. In addition, the ability of KET to reduce significantly a variety of nocifensive behaviors suggests that this clinically safe drug could be used in pain management for neuropathic patients.

The opposing effects of interleukin-1 β microinjected into the preoptic hypothalamus and the ventromedial hypothalamus on nociceptive behavior in rats

The effects of microinjections of recombinant human interleukin-1β (rhIL-1β) into the hypothalamus and neighboring basal forebrain on nociceptive behavior were studied using a hot-plate test in rats. The microinjection of rhIL-1β at doses between 5 pg/kg and 50 pg/kg into the medial part of the preoptic area (MPO) reduced the paw-withdrawal latency. The maximal reduction was obtained 30 min after the injection of rhIL-1β at 20 pg/kg. RhIL-1β (20 pg/kg)-induced hyperalgesia was completely blocked by the simultaneous injection of IL-1 receptor antagonist (IL-1ra, 20 ng/kg), Na salicylate (200 ng/kg) or α-melanocyte-stimulating hormone (α-MSH, 20 ng/kg). The intra-MPO injection of rhIL-1β at doses of less than 5 pg/kg or more than 50 pg/kg (up to 2 ng/kg) had no effect on nociceptive behavior. The microinjection of rhIL-1β (20 pg/kg) into the lateral part of the preoptic area, the median preoptic nucleus and the diagonal band of Broca also reduced the latency. On the other hand, the microinjection of rhIL-1β (20 pg/kg) into the paraventricular nucleus, the lateral hypothalamic area and the septal nucleus had no effect on nociception. The microinjection of rhIL-1β (20 pg/kg–50 pg/kg) into the ventromedial hypothalamus produced a prolongation of the paw-withdrawal latency. A maximal prolongation was obtained 10 min after the injection of rhIL-1β at 50 pg/kg. This reaction was also blocked by the simultaneous injection of IL-1ra (50 ng/kg) and Na salicylate (500 ng/kg). These findings indicate that IL-1β in the MPO and the VMH produces hyperalgesia and analgesia, respectively, while, in addition, both effects are mediated by IL-1 receptors and the synthesis of prostaglandins.

The role of NMDA receptor-operated calcium channels in persistent nociception after formalin-induced tissue injury

The contribution of intracellular calcium to central sensitization and persistent nociception in response to tissue injury in rats was examined following the subcutaneous injection of formalin into the hindpaw. Formalin injury-induced nociceptive behaviors were enhanced by intrathecal pretreatment with the calcium ionophore A23187 or the calcium channel agonist Bay-K8644. Conversely, formalin nociceptive responses were reduced by intrathecal pretreatment with the calcium chelator Quin 2 or the calcium channel antagonists verapamil and nifedipine. Each of these agents affected the tonic, but not the acute, phase of the formalin response. The enhancement in formalin nociceptive behavior in rats treated with L-aspartate or L-glutamate was reversed by combined pretreatment with the noncompetitive NMDA antagonist MK-801, but not by nifedipine or the non-NMDA excitatory amino acid antagonist 6-cyano-7-dinitroquinoxaline-2,3-dione. In rats not treated with excitatory amino acids, the analgesic effect of MK-801 was also significantly greater than that produced by nifedipine. Furthermore, combining nifedipine with MK-801 did not produce a significantly greater analgesic effect than MK-801 alone. The results suggest that central sensitization and persistent nociception following formalin-induced tissue injury are dependent on the influx of calcium through predominantly NMDA receptor-operated (and to a lesser extent voltage-gated) calcium channels.

Intrathecal GM1 ganglioside and local nerve anesthesia reduce nociceptive behaviors in rats with experimental peripheral mononeuropathy

Our previous experiments demonstrated that systemic treatment with GM1 ganglioside reduces nociceptive behaviors and spinal cord metabolic activity in a rat model of painful peripheral mononeuropathy produced by experimental sciatic nerve ligation (chronic constrictive injury, CCI). In the present study, we examined the effects of intrathecal (i.t.) GM1 treatment on thermal hyperalgesia and spontaneous pain behaviors resulting from nerve ligation in order to determine the locus of GM1 action. In addition, a local agesthetic agent, bupivacaine, given alone or combined with i.t. GM1, was applied to the injured sciatic nerve to determine if peripheral nerve anesthesia would influence post-injury nociceptive behaviors. Thermal hyperalgesia to radiant heat decreased in a dose-dependent manner when GM1 (10–80 nmol, i.t.) was administered once daily onto the lumbar segments of the spinal cord beginning 1 h after experimental nerve injury and continued for the first 9 days after nerve ligation. Moreover, this GM1 (80 nmol) treatment regimen reliably lowered spontaneous pain behavior rating scores in CCI rats suggesting the possible attenuation of spontaneous pain. The central site of i.t. GM1 action is located at the caudal (probably lumbar) spinal cord, since i.t. injection of 20 nmol GM1 onto the cervical spinal cord dit not produce any protective effect. A single perinerve injection of a local anesthetic agent, bupivacaine (0.5%, 0.6 ml), on the 3rd day after nerve ligation reduced thermal hyperalgesia for at least 24 h following injection, a duration longer than that of the local anesthetic action of bupivacaine. Neither a single bupivacaine injection nor four daily i.t. GM1 injections (20 nmol) initiated 1 h after nerve ligation attenuated thermal hyperalgesia for a duration longer than 2 days after the final injection. However, the combination of these two treatments decreased thermal hyperalgesia for at least 4 days the injection. This result suggests that these two manipulations may be useful for the clinical management of chronic post-injury neuropathic pain syndromes. These results also indicate that both peripheral and central mechanisms contribute to nociceptive behaviors that occur following peripheral nerve injury. The mechanism of GM1 action is discussed with emphasis on possible attenuation of post-injury neurotoxicity mediated by excitatory amino acids.

Contribution of protein kinase C to central sensitization and persistent pain following tissue injury.

This paper provides evidence that central sensitization and persistent nociception following formalin-induced tissue injury in rats is dependent on the production of protein kinase C. Persistent nociceptive behavior in rats induced by subcutaneous formalin injection was significantly reduced by intrathecal pretreatment with a phospholipase C inhibitor (neomycin), and an inhibitor of protein kinase C (W-7), and was significantly enhanced by a phorbol ester (phorbol 12-myristate 13-acetate, PMA) and a stimulator of protein kinase C (SC-10). It is expected that noxious inputs associated with tissue injury produce a release of aspartate and glutamate within the spinal dorsal horn which by acting at ionotropic (NMDA) and metabotropic excitatory amino acid receptors produce an increase in intracellular messengers such as calcium and diacylglycerol which stimulate protein kinase C.

Intrathecal MK-801 and local nerve anesthesia synergistically reduce nociceptive behaviors in rats with experimental peripheral mononeuropathy

The hyperalgesia and spontaneous pain that occur following peripheral nerve injury may be related to abnormal peripheral input or altered central activity, or both. The present experiments investigated these possibilities by examining the effects of MK-801 (a non-competitive N-methyl- d-aspartate, NMDA, receptor antagonist) and bupivacaine (a local anesthetic agent) on thermal hyperalgesia and spontaneous nociceptive behaviors in rats with painful peripheral mononeuropathy. Peripheral mononeuropathy was produced by loosely ligating the rat's common sciatic nerve, a procedure which causes chronic constrictive injury (CCI) of the ligated nerve. The resulting hyperalgesia to radiant heat and spontaneous nociceptive behaviors was assessed by using a foot-withdrawal test and a spontaneous pain behavior rating method, respectively. CCI rats receiving 4 daily intraperitoneal (i.p.) MK-801 injections (0.03, 0.1, 0.3 mg/kg) beginning 15 min prior to nerve ligation exhibited less hyperalgesia (i.e., longer foot-withdrawal latencies) on days 3, 5, 7, 10, and 15 after nerve ligation as compared to those receiving saline injections. Thermal hyperalgesia also was reduced when a single MK-801 injection was given intrathecally (i.t.) onto the spinal cord lumbar segments on Day 3 after nerve ligation. This effect of postinjury MK-801 treatment was dose-dependent (2.5 – 20 nmol) and lasted for at least 48 h after injection. Moreover, i.t. injection of MK-801 (10 nmol) reliably lowered spontaneous pain behavior rating scores in CCI rats compared to those in the saline group. The spinal site of MK-801 action is situated within the caudal (probably lumbar) spinal cord, since i.t. injection of MK-801 (10 nmol) onto the spinal cord thoracic segments did not affect thermal hyperalgesia. Local anesthesia of the ligated sciatic nerve induced by a single perinerve bupivacaine injection on Day 3 after nerve ligation reliably reduced thermal hyperalgesia when tested 24 h after injection, indicating that abnormal peripheral input contributes to maintenance of neuropathic pain. While i.t. MK-801 (2.5 nmol) or local nerve anesthesia on Day 3 after nerve ligation attenuated thermal hyperalgesia for less than 48 h after injection, the combined application of MK-801 and bupivacaine extended the duration of the attenuation of thermal hyperalgesia for at least 4 days after injection. The data indicate that the central blockade of NMDA receptors and peripheral nerve anesthesia synergistically attenuate nociceptive behaviors associated with peripheral mononeuropathy. The results suggest that hyperalgesia and spontaneous pain behaviors following constrictive nerve injury may be related to both abnormal peripheral input and altered central activity involving NMDA receptor activation. These results also suggest novel approaches to the clinical management of postinjury neuropathic pain syndromes.

Modifiability of spinal synapses.

Modifiability of spinal synapses.

Functional relationships between neurons of marginal and substantia gelatinosa layers of primate dorsal horn

ArticlesFunctional relationships between neurons of marginal and substantia gelatinosa layers of primate dorsal hornD. D. Price, H. Hayashi, R. Dubner, and M. A. RudaD. D. Price, H. Hayashi, R. Dubner, and M. A. RudaPublished Online:01 Nov 1979https://doi.org/10.1152/jn.1979.42.6.1590MoreSectionsPDF (4 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited BySpinal Circuits Transmitting Mechanical Pain and Itch8 May 2017 | Neuroscience Bulletin, Vol. 34, No. 1Spinal dorsal horn neurone targets for nociceptive primary afferents: do single neurone morphological characteristics suggest how nociceptive information is processed at the spinal levelBrain Research Reviews, Vol. 46, No. 2Correlation of functional activation in the rat spinal cord with neuronal activation detected by immunohistochemistryNeuroImage, Vol. 22, No. 4Neurons involved in the exteroceptive function of painPain, Vol. 106, No. 3Exogenous Tumor Necrosis Factor-α Induces Abnormal Discharges in Rat Dorsal Horn NeuronsSpine, Vol. 27, No. 15C Fiber Responses of Wide Dynamic Range Neurons in the Spinal Dorsal HornClinical Orthopaedics and Related Research, Vol. 349Encoding of Corneal Input in Two Distinct Regions of the Spinal Trigeminal Nucleus in the Rat: Cutaneous Receptive Field Properties, Responses to Thermal and Chemical Stimulation, Modulation by Diffuse Noxious Inhibitory Controls, and Projections to the Parabrachial AreaI. D. Meng, J. W. Hu, A. P. Benetti, and D. A. Bereiter1 January 1997 | Journal of Neurophysiology, Vol. 77, No. 1Sensitization of high mechanothreshold superficial dorsal horn and flexor motor neurones following chemosensitive primary afferent activationPain, Vol. 58, No. 2Short-term plasticity in turtle dorsal horn neurons mediated by L-type Ca2+ channelsNeuroscience, Vol. 61, No. 2Neurons in the superficial dorsal horn of the rat spinal cord projecting to the medullary ventrolateral reticular formation express c-fos after noxious stimulation of the skinBrain Research, Vol. 623, No. 2Emerging relationships between cytochemical properties and sensory modality transmission in primary sensory neuronsBrain Research Bulletin, Vol. 30, No. 3-4Reply to F. CerveroPain, Vol. 51, No. 2Intrathecal MK-801 and local nerve anesthesia synergistically reduce nociceptive behaviors in rats with experimental peripheral mononeuropathyBrain Research, Vol. 576, No. 2Microinjections of norepinephrine within the superficial laminae of trigeminal subnucleus caudalis evoke increases in plasma adrenocorticotropin in the ratBrain Research, Vol. 568, No. 1-2The spino-latero-reticular system of the rat: Projections from the superficial dorsal horn and structural characterization of marginal neurons involvedNeuroscience, Vol. 45, No. 1Evidence that substance P selectively modulates C-fiber-evoked discharges of dorsal horn nociceptive neuronsBrain Research, Vol. 526, No. 2Electrical stimulation reveals relatively ineffective sural nerve projections to dorsal horn neurons in the catBrain Research, Vol. 371, No. 1Selective reduction of second pain sensations by systemic morphine in humansPain, Vol. 24, No. 1A psychophysical analysis of morphine analgesiaPain, Vol. 22, No. 3Ultrastructural study of neurotensin immunoreactivity in the superficial laminae of the dorsal horn of the ratPeptides, Vol. 5, No. 6Receptive fields and responses to ionophoretically applied nonradrenaline and 5-hydroxytryptamine of units recorded in laminae I–III of cat dorsal hornBrain Research, Vol. 288, No. 1-2Basic neurobiologic mechanisms of pain and analgesiaThe American Journal of Medicine, Vol. 75, No. 5Responses of substantia gelatinosa neurons to putative neurotransmitters in an in vitro preparation of the adult rat spinal cordBrain Research, Vol. 279, No. 1-2Location and functional organization of trigeminal wide dynamic range neurons within the nucleus ventralis posteromedials of the catNeuroscience Letters, Vol. 39, No. 3Somatotopic distribution of trigeminal nociceptive specific neurons within the caudal somatosensory thalamus of catNeuroscience Letters, Vol. 39, No. 2Influences of contralateral nerve and skin stimulation on neurones in the substantia gelatinosa of the rat spinal cordNeuroscience Letters, Vol. 36, No. 2Chronic peripheral nerve section diminishes the primary afferent A-fibre mediated inhibition of rat dorsal horn neuronesBrain Research, Vol. 242, No. 1The cytoarchitecture of gabaergic neurons in rat spinal cordBrain Research, Vol. 238, No. 2The responses of neurones of the superficial dorsal horn to ionophoretically applied glutamate ionBrain Research, Vol. 231, No. 2Intrathecal substance P and somatostatin in rats: Behaviors indicative of sensationPeptides, Vol. 3, No. 1A Study of the cutaneous afferent input to substantia gelatinosaNeuroscience, Vol. 6, No. 11An immunohistochemical study of neuronal populations containing neuropeptides or γ-aminobutyrate within the superficial layers of the rat dorsal hornNeuroscience, Vol. 6, No. 10Spinal cord layer I neurons with axon collaterals that generate local arborsBrain Research, Vol. 209, No. 2Descending influences on receptive fields and activity of single units recorded in laminae 1, 2 and 3 of cat spinal cordBrain Research, Vol. 199, No. 2Raphe and periaqueductal gray induced suppression of non-nociceptive neuronal responses in the dorsal column nuclei and trigeminal sub-nucleus caudalisBrain Research, Vol. 200, No. 1The substantia gelatinesa. A gate control mechanism set across a sensory pathwayTrends in Neurosciences, Vol. 3, No. 9 More from this issue > Volume 42Issue 6November 1979Pages 1590-1608 Copyright & PermissionsCopyright © 1979 the American Physiological Societyhttps://doi.org/10.1152/jn.1979.42.6.1590PubMed228014History Published online 1 November 1979 Published in print 1 November 1979 Metrics