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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Central pain syndromes (CPS) could be caused by disinhibition of spinothalamic excitability or by other central nervous system (CNS) changes caused by reduced spinothalamic function. To examine these possibilities, we studied 11 patients (ages 51-82 years) with unilateral central pain and with reproducible cerebral evoked vertex potentials in response to cutaneous stimulation of the normal side with pulses from an infra-red CO2 laser. All patients had normal tactile and kinesthetic sensation; one had slightly decreased vibratory sense bilaterally. All showed, from the unaffected (asymptomatic) side, laser evoked potentials (LEPs) with negative (N) components ranging from 208 to 280 msec peak latency (av: 240 +/- 6 SE msec) and peak amplitudes of 1-7 microV (av: 2.9 +/- 0.5 SE microV), followed, in all but 1 patient, by positive (P) potentials ranging from 288 to 370 msec peak latency (av: 319 +/- 7.7 SE msec) with peak amplitudes of 1-7 microV (2.8 +/- 0.5 SE microV). Laser stimulation of the affected (symptomatic) side in 5 patients evoked LEPs with N-P interpeak amplitudes that were within 20% of those evoked from the normal side. All but one of these patients had thresholds for warm, heat pain, and deep pain that were normal in comparison with the unaffected side. The excepted patient had the largest N-P interpeak amplitude asymmetry (18.5%) of this group. Ratings of laser pulse intensity were either symmetrical (n = 2) or increased on the affected side (n = 3) in these patients. In contrast, laser stimulation of the affected side failed to evoke either N or P potentials in 6 patients, all of whom had lateralized increased thresholds for warm, heat pain, or deep pain, or reduced ratings of laser pulse sensation. Although 1 patient had increased ratings of laser pulse sensation, the amplitude of the LEP was always reduced on the side of increased pain or heat threshold in these CPS patients (Fisher exact test: P = 0.015). These results reflect primarily a deficit in spinothalamic tract function and do not suggest excessive CNS responses to synchronous activation of cutaneous heat nociceptors in patients with CPS.
Pain 1996 Mar
PMID:Laser-evoked cerebral potentials and sensory function in patients with central pain. 878 13

Touch evoked agitation (allodynia) can be induced by spinal delivery of strychnine and this effect is antagonized by intrathecal NMDA and non-NMDA receptor antagonists, but not by mu-opiate receptor agonists. In this study, we sought to characterize the effect of focal glycine-receptor inhibition on spontaneous and evoked activity in dorsal horn neurons of the chloralose-anesthetized cat. Strychnine (1 mM) applied near the neurons through a dialysis fiber caused an enhanced response to hair deflection, enlargement of the low threshold receptive fields and in some cells, an increase in afterdischarge. These changes were observed only in cells that were activated by both hair deflection and high intensity mechanical stimulation. Subsequent co-administration of an NMDA receptor antagonist (AP-7, 2.0 mM) preferentially blocked strychnine-associated effects without changing the original receptive field characteristics. Co-administration of a non-NMDA excitatory amino acid receptor antagonist (CNQX, 1 mM) with the strychnine served to block low (brush) and high intensity (pinch) afferent input. In contrast, addition of a mu-opiate receptor agonist (alfentanil 2.4 mM) to the strychnine perfusate selectively reduced responsiveness to high intensity stimulation, while having no effect on the exaggerated response to hair deflection. Given the functional and pharmacological similarity of the effects of spinal strychnine to post-nerve injury states in man, disinhibition due to a loss of glycinergic input may be associated with large myelinated fiber-mediated nociceptive states. Consistent with these data is the contention that under normal circumstances, afferent hair follicle input onto convergent neurons is regulated by a tonic glycinergic circuit. Removal of this regulatory influence leads to a magnification of low threshold tactile throughput in dorsal horn. This model may help to provide pharmacological insights into more efficacious treatments for such pain states that are relatively refractory to opioid therapies.
Pain 1996 Dec
PMID:Neuronal model of tactile allodynia produced by spinal strychnine: effects of excitatory amino acid receptor antagonists and a mu-opiate receptor agonist. 912 16

This study, addressing etiologic and pathogenic aspects of fibromyalgia (FM), aimed at examining whether sensory abnormalities in FM patients are generalized or confined to areas with spontaneous pain. Ten female FM patients and 10 healthy, age-matched females participated. The patients were asked to rate the intensity of ongoing pain using a visual analogue scale (VAS) at the site of maximal pain, the homologous contralateral site and two homologous sites with no or minimal pain. Quantitative sensory testing was performed for assessment of perception thresholds in these four sites. Von Frey filaments were used to test low-threshold mechanoreceptive function. Pressure pain sensitivity was assessed with a pressure algometer and thermal sensitivity with a Thermotest. In addition the stimulus-response curve of pain intensity as a function of graded nociceptive heat stimulation was studied at the site of maximal pain and at the homologous contralateral site. FM patients had increased sensitivity to non-painful warmth (P < 0.01) over painful sites and a tendency to increased sensitivity to non-painful cold (P < 0.06) at all sites compared to controls, but there was no difference between groups regarding tactile perception thresholds. Compared to controls, patients demonstrated increased sensitivity to pressure pain (P < 0.001), cold pain (P < 0.001) and heat pain (P < 0.02) over all tested sites. The stimulus-response curve was parallely shifted to the left of the curve obtained from controls (P < 0.003). Intragroup comparisons showed that patients had increased sensitivity to pressure pain (P < 0.01) and light touch (P < 0.05) in the site of maximal pain compared to the homologous contralateral site. These findings could be explained in terms of sensitization of primary afferent pathways or as a dysfunction of endogenous systems modulating afferent activity. However, the generalized increase in sensitivity found in FM patients was unrelated to spontaneous pain and thus most likely due to a central nervous system (CNS) dysfunction. The additional hyperphenomena related to spontaneous pain are probably dependent on disinhibition/facilitation of nociceptive afferent input from normal (or ischemic) muscles.
Pain 1996 Dec
PMID:Sensory dysfunction in fibromyalgia patients with implications for pathogenic mechanisms. 912 27

1. Intrathecal (i.t.) administration of nociceptin and high doses of morphine induced allodynia in response to innocuous tactile stimuli, and i.t. nociceptin evoked hyperalgesia in response to noxious thermal stimuli in conscious mice. Here we have characterized the nociceptin-induced allodynia and compared it with the morphine-induced allodynia and the nociceptin-evoked hyperalgesia. 2. Nociceptin-induced allodynia was evoked by the first stimulus 5 min after i.t. injection, reached a maximum at 10 min, and continued for a 50 min experimental period. Dose-dependency of the allodynia showed a bell-shaped pattern from 50 pg to 5 ng kg-1, and the maximum effect was observed at 2.5 ng kg-1. 3. Morphine-induced allodynia reached the maximum effect at 15 min and declined progressively until cessation by 40-50 min. The dose-response curve showed a bell-shaped pattern, similar to that induced by nociceptin, with a maximum effect at 0.5 mg kg-1, five orders of magnitude higher than that of nociceptin. 4. The allodynia evoked by nociceptin and morphine were dose-dependently blocked by glycine, D(-)-2-amino-5-phosphonovaleric acid (D-AP5, an N-methyl-D-aspartate (NMDA) receptor antagonist), gamma-D-glutamylaminomethyl sulphonic acid (GAMS, a non-NMDA receptor antagonist) and methylene blue (a soluble guanylate cyclase inhibitor), but were not affected by muscimol (a gamma-aminobutyric acidA (GABAA) receptor agonist) and baclofen (a GABAB receptor agonist). 5. Morphine did not inhibit forskolin-stimulated cyclicAMP formation in cultured cells expressing the nociceptin receptor. 6. Nociceptin-induced hyperalgesia was evoked 10-15 min after i.t. injection. Nociceptin produced a monophasic hyperalgesic action over a wide range of doses from 5 fg to 50 ng kg-1. The nociceptin-induced hyperalgesia was blocked by glycine only among the agents examined. 7. None of the pain responses evoked by nociceptin and morphine were blocked by naloxone. 8. These results demonstrate that, whereas the mechanisms of the nociceptin-induced allodynia and hyperalgesia are evidently distinct, they involve a common neurochemical event beginning with the disinhibition of the inhibitory glycinergic response. Morphine may induce allodynia through a pathway common to nociceptin, but the nociceptin receptor does not mediate the action of high doses of morphine.
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PMID:Characterization of nociceptin hyperalgesia and allodynia in conscious mice. 917 80

After the administration of 11 mg/kg of sodium nitrite (NO of the generating drug) the motor disinhibition and increase in the myogram amplitude were observed in reaction of rabbits to non-reinforced flashes at the background of continuous light which served as a conditioned inhibitory signal (CIS). The disinhibition appeared within 1-1.5 h from he moment of NO administration and continued during the whole recording period (4 h). Under the NO dose of 5.5 mg/kg only the tendency was observed to motor disinhibition after the CIS presentation. The results obtained can be possibly explained by the NO ability to inhibit the functions of the GABA-ergic receptors, since it is known that elaboration of the internal inhibition is accompanied by an enhancement of the inhibitory hyperpolarizing processes realized with participation of the GABA-ergic transmitter system. Under the action on NO both in the small and doubled doses the myogram amplitude did not increase in response to combined presentation of the light flashes with pain reinforcement, in contrast to the repeated presentations of these paired stimuli in the control experiments. This phenomenon is probably determined by the inhibitory influence of NO on the NMDA receptors.
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PMID:[The effect of sodium nitrite on the realization of defensive and inhibitory conditioned reflexes]. 918 27

Experiments in both conscious and anesthetized animals indicate that intrathecal (i.t.) strychnine (STR; glycine receptor antagonist) produces acute, reversible allodynia, as evidenced by inappropriate behavioral and autonomic responses to cutaneous tactile stimuli. Although STR is known to produce disinhibition of afferent input to the spinal cord, changes in spinal reflexes cannot fully explain the complex behaviors observed following i.t. STR. Which supraspinal sites are involved in STR-dependent allodynia and how this abnormal somatosensory message is relayed to these sites remain to be determined. The medial thalamus contains many nociceptive-specific (NS) neurons and is believed to be involved in mediating the affective-motivational aspects of pain. It is thus important to determine whether spinally administered STR elicits changes in the responses of medial thalamic NS neurons. Extracellular single-unit recordings were conducted in urethan-anesthetized rats (290-490 g). A detailed characterization of 20 thalamic NS units (1 per rat; 2 in 1 case) was conducted before and immediately after i.t. STR (40 microg). Initially, all of the units in this study were classified as NS, because they were excited by noxious pinch but not by innocuous tactile stimuli. After i.t. STR, all (formerly NS) units exhibited significant responses to innocuous tactile stimuli (brush and/or air jet) applied to lumbar or sacral dermatomes. This effect of STR on thalamic NS neurons was acute and reversible. The majority of units (11 of 20) also exhibited an increase in spontaneous firing rate. Although the complete pinch receptive field (RF) could not be determined for all units, the available data indicate that the RFs for brush stimulation after i.t. STR were substantially different from the pre-STR pinch RFs for all but three units. The same i.t. STR injection that caused the observed changes in medial thalamus also produced allodynia, in the form of brush-evoked cardiovascular or motor responses, in 18 of the 19 rats. The ability of NS cells in medial thalamus to respond to tactile input after i.t. STR suggests that the STR lowers the threshold of nociceptive neurons that project directly and/or indirectly to medial thalamus. These observations suggest that ascending nociceptive pathways and medial thalamic structures contribute to the expression of STR-dependent allodynia.
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PMID:Spinal strychnine alters response properties of nociceptive-specific neurons in rat medial thalamus. 930

The effects of selective tonic cutaneous and muscle pain stimulation on heteronymous Ib pathways from the gastrocnemius medialis to the soleus motoneurones were studied in five healthy human subjects. Tonic pain stimulation, monitored by a psychophysical method, was obtained by local injection of 60 mg levo-ascorbic acid (L-AS) in a volume of 0.3 ml. Nociceptive cutaneous and muscle stimulation of the dorsal foot produced opposite, long-lasting changes in heteronymous Ib pathways to soleus motoneurones: Ib facilitation during cutaneous stimulation was reversed by disinhibition during muscle stimulation. The time-course of these Ib changes strictly paralleled that of subjective pain sensation. On the contrary, when the same nociceptive stimuli were applied to the leg (at pretibial level), the differences between cutaneous and muscle pain disappeared and similar short-lasting phases of facilitation and inhibition of Ib activity were observed. It is concluded that tonic discharge of cutaneous and muscle nociceptive afferents arising from the foot have specific and opposite effects on Ib inhibitory pathways to ankle extensor motoneurones. These interactions between muscle and cutaneous nociceptive and Ib pathways may be used to change muscle synergies, thus contributing to the establishment of appropriate adaptive locomotor strategies during pain.
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PMID:Changes in Ib heteronymous inhibition to soleus motoneurones during cutaneous and muscle nociceptive stimulation in humans. 945 92

Sensitization is manifested as an increased response of neurones to a variety of inputs following intense or noxious stimuli. It is one of the simplest forms of learning and synaptic plasticity and it represents an important feature of nociception. In the spinal cord, repeated stimulation (at constant strength) of dorsal root afferents including nociceptive C fibres can elicit a progressive increase in the number of action potentials generated by motoneurones and interneurones. This phenomenon is termed "action potential windup" and is used as a cellular model of pain sensitization developing at the level of the central nervous system. Understanding the mechanisms responsible for windup generation might allow clarification of the cellular mechanisms of pain signalling and development of new strategies for pain treatment. Action potential windup is observed in a minority of cells only, indicating that certain cell-specific mechanisms are responsible for its generation. The most reliable index to predict windup generation is the rate at which the membrane potential is depolarized during repetitive stimulation. This phenomenon has been proposed to be due to gradual recruitment of NMDA receptor activity, to summation of slow excitatory potentials mediated by substance P (and related peptides) or to facilitation of slow calcium channels by metabotropic glutamate receptors. Little is known about the role of synaptic inhibition in windup, although it should not be underestimated. Each theory per se is unable to account for all the experimental observations. Since NMDA receptors are involved in many forms of synaptic plasticity, additional mechanisms such as summation of slow peptidergic potentials, facilitation of slow Ca2+ currents and disinhibition are proposed as necessary to impart specificity to pain-induced sensitization. These additional mechanisms might be species specific and change during development or chronic pain states.
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PMID:Sensitization of pain pathways in the spinal cord: cellular mechanisms. 948 3

Psychophysical methods were used to investigate pain in human subjects elicited by controlled freezing of the skin using a novel vortex thermode. When cooling stimuli delivered with a small thermode (7 mm diameter) exceeded the normal cold pain threshold into the sub-zero temperature range (-5 to -11 degrees C), all subjects reported an intense, sharp stinging pain sensation which occurred suddenly and was readily differentiated from normal cold pain. The onset of this stinging 'freezing' pain was closely correlated with a sudden increase in skin temperature beneath the thermode of 4.77+/-0.86 degrees C (+/-SD) associated with the phase transition of supercooled water to ice. The mean intensity of freezing pain was rated as 1.7 times as intense as cold pain at threshold. Subjects' mean reaction-time latency to signal stinging pain following the onset of phase transition on the volar forearm was 687+/-220 ms, which was slower than that for mechanically evoked impact pain. Freezing pain is suggested to be mediated by A-delta fibers, based on estimates of conduction velocity and on the observation that the freezing pain took on a burning quality of slower onset during an A-fiber pressure block of nerve fibers. We also investigated changes in skin sensation following the freezing stimulus, and found that freezing led to (a) an immediate, significant decrease in the cold pain threshold (to higher temperatures), which recovered to baseline in < 16 min, (b) a concomitant change in the quality of cold pain from dull to burning, (c) a significant, parallel increase in the threshold for the perception of cooling (to lower temperatures) which frequently manifested as a complete loss of cold sensation, and (d) a mild heat pain hyperalgesia which was still present 24 h later. The changes in thermal sensitivity were not accompanied by consistent changes in mechanical sensitivity. These results indicate that a characteristic sharp, stinging pain is reliably evoked abruptly at the phase transition of supercooled skin water to ice The ensuing brief decrease in cold pain threshold with burning quality, coupled with decreased sensitivity to cold, are speculated to reflect a central disinhibition of C-fiber nociceptor input due to reduced cold fiber activity. These effects may be relevant to frostbite, and distinguish themselves from the more pronounced thermal and mechanical hyperalgesia seen following intense freeze lesion of the skin.
Pain 1998 Feb
PMID:Psychophysical study of stinging pain evoked by brief freezing of superficial skin and ensuing short-lasting changes in sensations of cool and cold pain. 952 Feb 42

Microinjection of baclofen, a gamma-aminobutyric acidB (GABA[B]) receptor agonist, in the nucleus raphe magnus (NRM) or nucleus reticularis gigantocellularis pars alpha (NGCpalpha) of the rat produces antinociception at doses of 0.1-1.0 ng and hyperalgesia at doses of 30-150 ng in the tail-flick test. The antinociception is proposed to result from disinhibition of spinally-projecting neurons in this region that contain serotonin. The hyperalgesia is proposed to result either from inhibition of these neurons or from disinhibition of a serotonergic pain facilitatory pathway that also originates in this area of the ventromedial medulla. To determine the involvement of bulbospinal serotonergic pathways in the biphasic effects of baclofen, rats were pretreated intrathecally with either 30 microg of methysergide or saline. Ten minutes later, either saline, 0.5 ng or 150 ng of baclofen was microinjected in the NRM and NGCpalpha, and alterations in nociceptive threshold were assessed by the tail-flick and hot-plate tests. Intrathecal pretreatment with methysergide prevented the increase in tail-flick latency produced by 0.5 ng of baclofen, but did not prevent the decrease in tail-flick latency produced by 150 ng of baclofen. Neither dose of baclofen altered hot-plate latency and this lack of effect was unchanged by methysergide. These data support the idea that the antinociceptive effect of low doses of baclofen in the tail-flick test is mediated by disinhibition of a bulbospinal serotonergic projection and release of serotonin in the spinal cord. These data also suggest that the hyperalgesia produced by high doses of baclofen does not result from disinhibition of a serotonergic pain facilitatory pathway, but rather from direct inhibition of tonically-active pain inhibitory neurons in the NRM and NGCpalpha.
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PMID:Intrathecal methysergide antagonizes the antinociception, but not the hyperalgesia produced by microinjection of baclofen in the ventromedial medulla of the rat. 957 93


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