Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Substance P, 5-hydroxytryptamine, and gamma-aminobutyric acid levels in saliva were measured in 55 patients with migraine during headache attacks (15 men and 40 women, average age 37.6 years), 36 patients with migraine in interictal periods (8 men and 28 women, average age 43.9 years), 48 patients with tension-type headache during headache attacks (18 men and 30 women, average age 47.3 years), and 25 patients with tension-type headache in interictal periods (10 men and 15 women, average age 48.6 years). Forty-three normal healthy volunteers composed the control group (17 men and 26 women, average age 32.7 years). Substance P levels in saliva were determined using competitive enzyme-linked immunosorbent assay, and were 26.9 +/- 45.1 pmol/mL in the patients with migraine during headache attacks, 30.0 +/- 59.7 pmol/mL in the patients with migraine in interictal periods, 243.5 +/- 1137 pmol/mL in the patients with tension-type headache during headache attacks, 101.3 +/- 364 pmol/mL in the patients with tension-type headache in interictal periods, and 21.2 +/- 17.4 pmol/mL in the healthy controls. 5-hydroxytryptamine levels in saliva were determined using reversed-phase high-performance liquid chromatography with electrochemical detection, and were 895 +/- 1075 ng/mL in the patients with migraine during headache attacks, 758 +/- 1375 ng/mL in the patients with migraine in interictal periods, 1646 +/- 1945 ng/mL in the patients with tension-type headache during active headache periods, 1167 +/- 1495 ng/mL in the patients with tension-type in headache-free periods, and 450 +/- 405 ng/mL in the healthy controls. Gamma-aminobutyric acid levels in saliva were determined using high-performance liquid chromatography with precolumn ortho-phthalaldehyde fluorescence detection. Gamma-aminobutyric acid levels in saliva were 36.8 +/- 49.8 pmol/mL in the patients with migraine during headache attacks, 17.9 +/- 25.2 pmol/mL in the patients with migraine in interictal periods, 16.0 +/- 18.3 pmol/mL in the patients with tension-type headache during active headache periods, 14.1 +/- 6.8 pmol/mL in the patients with tension-type headache in headache-free periods, and 21.6 +/- 22.7 pmol/mL in the healthy controls. The salivary substance P and 5-hydroxytryptamine levels in the patients with tension-type headache during active headache periods were significantly higher than those in healthy controls. In contrast, we found no significant differences between the salivary gamma-aminobutyric acid levels in the patients with tension-type headache and healthy controls. The high levels of salivary substance P and 5-hydroxytryptamine in tension-type headache patients during headache periods might reflect release of substance P from the pain sensory system. Saliva could represent a fluid particularly suitable to the study of neuropeptide release under specific conditions such as migraine and tension-type headache.
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PMID:Salivary substance P, 5-hydroxytryptamine, and gamma-aminobutyric acid levels in migraine and tension-type headache. 874 82

Progesterone (P), its metabolites, and other neuroactive steroids alter pain thresholds consistent with their efficacies at modulating gamma-aminobutyric acid (GABAA) receptor complexes. We investigated whether estradiol benzoate (EB) potentiates low dosages of neuroactive steroids' effects on pain. Subcutaneous EB (10 micrograms) or sesame oil vehicle was administered to ovariectomized Long-Evans rats (n = 40) 48 h before intracerebroventricular (ICV) infusion of a neuroactive steroid (0.0, 0.1, 0.3, or 0.5 micrograms) in cyclodextrin vehicle. Neuroactive steroids (listed from greatest to least efficacious at GABAA receptor complexes) were THP [5 alpha-pregnan-3 alpha-ol-20-one], THDOC [5 alpha-pregnan-3 alpha, 21-diol-20-one], DHP [5 alpha-pregnan-3,20-dione], P [4-pregnen-3,20-dione], and DHEAS [5-androsten-3 beta-ol-17-one sulfate]. Pain sensitivity was assessed using the radiant heat tail-flick method before and 20 and 60 min following infusion. Estradiol benzoate interacted with the neuroactive steroids to alter tail-flick latencies. In particular, EB potentiated the antinociceptive effect of THP and DHP by significantly increasing tail-flick latencies above those of non-EB-treated animals. A similar pattern of increased tail-flick latencies occurred in EB-primed animals that received THDOC. Estradiol benzoate less consistently altered the pain threshold of animals administered P, which is less effective at modulating GABAergic activity. Conversely, EB increased the nociceptive effect of the neurosteroid DHEAS, an allosteric antagonist of GABAA receptor complexes, by significantly decreasing tail-flick latencies of EB-compared to vehicle-primed rats. Thus, EB priming potentiated neuroactive steroids' effects on pain threshold.
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PMID:Estradiol benzoate potentiates neuroactive steroids' effects on pain sensitivity. 884 56

The current study was designed to determine if the monoaminergic descending inhibitory system and the glycinergic and GABAergic inhibitory systems were activated in the spinal cord in the presence of peripheral mononeuropathy produced by loose ligatures around the common sciatic nerve. The time course of withdrawal latencies to thermal stimuli were assayed in lesioned and sham-operated rats. The levels of monoamines (serotonin; 5-HT, noradrenaline, and dopamine), glycine and gamma-aminobutyric acid (GABA) in the dorsal half of the spinal cord were measured using HPLC with electrochemical detection. Furthermore, on day 7 after nerve ligation, intrathecal methysergide, yohimbine, strychnine or bicuculline was administered in order to investigate the roles of these inhibitory neuromodulators in this pathological pain state. The levels of 5-HT and noradrenaline significantly increased in both ipsi- and contralateral sides of the dorsal half of the lumbar spinal cord in the lesioned, but not sham-operated animals. The levels of glycine and GABA in the ipsilateral dorsal half of the spinal cord increased significantly and were significantly higher than in the contralateral side. Intrathecal antagonists of 5-HT, noradrenaline, glycine and GABA produced enhancement of the magnitude of hyperalgesia on the lesioned hindpaw. We also examined the effects of four daily single treatments with intrathecal MK-801 beginning 15 min prior to nerve ligation on the development of thermal hyperalgesia and on the contents of the neuromodulators in the ligation model. MK-801 treatment effectively abolished the increases in 5-HT, noradrenaline, glycine and GABA levels as well as preventing the development of hyperalgesia. The results of the present study suggest that the pathological pain state activates or increases the activity of these inhibitory systems.
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PMID:Roles of monoaminergic, glycinergic and GABAergic inhibitory systems in the spinal cord in rats with peripheral mononeuropathy. 886 94

Baclofen, an agonist of the gamma-aminobutyric acid (GABA) receptor, has antinociceptive effects, and its intrathecal administration reduces allodynic responses in animal models of neurogenic central pain. Such experimental studies lead to the hypothesis that neurogenic pain may be induced in part by functional abnormalities in spinal GABAergic systems. However, whether a GABAergic system is actually involved in human central pain is unknown. The authors investigated the effect of an intrathecal bolus injection of baclofen in 14 patients with central pain due to a stroke or spinal cord injury. Nine reported substantial pain relief they had never experienced previously. The effect appeared 1-2 h after the injection and persisted for 10-24 h. Allodynia and hyperalgesia, if present, were relieved as well. Pinprick and light touch sensations did not change in nonaffected regions. The results indicate that dysfunction of spinal GABAergic systems plays a role in the clinical expression of central pain. In clinical situations, continuous intrathecal infusion of baclofen seems feasible for relief of central pain.
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PMID:A new approach to control central deafferentation pain: spinal intrathecal baclofen. 891 36

Gamma-aminobutyric acid (GABA) receptors are ubiquitous inhibitory receptors in the central and peripheral nervous systems. Valproic acid (2-propylpentanoic acid), which enhances GABA synthesis and blocks degradation, is useful in migraine treatment and may act through activation of GABA receptors to modulate trigeminal nociceptive neurons innervating the meninges. To investigate this possibility, we tested the effect of valproate and allopregnanolone, a metabolite of progesterone, which binds and modulates the GABA receptor in an animal model of cephalic pain. One hundred ten Hartley guinea pigs were pretreated with either valproate or allopregnanolone 30 minutes prior to activation of trigeminal afferent fibers via intracisternal injection of the irritant, capsaicin. The effects of valproic acid and allopregnanolone were examined on c-fos expression within the trigeminal nucleus caudalis (lamina I, II), the termination site for small unmyelinated C fibers projecting from the meninges. C-fos positive cells were counted at three representative levels (rostral, middle, and caudal) by an observer naive to the treatment group. We found that valproate (> or = 10 mg/kg, IP) reduced labeled cells by 52% (P < 0.05) and allopregnanolone (> or = 100 mg/kg, IP) reduced labeled cells by 42% (P < 0.01). Bicuculline (GABAA antagonist), but not phaclofen (GABAB antagonist), blocked the valproate effect, thereby documenting the importance of GABAA receptors. We conclude that the attenuation of c-fos-LI by valproate and allopregnanolone is mediated via GABAA receptors. These studies complement prior experiments showing that valproic acid and allopregnanolone block neurogenic inflammation within the meninges via GABAA receptor-mediated mechanisms. The findings suggest a potential strategy for discovering new antimigraine drugs with high affinity for the GABAA receptor and its modulatory sites.
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PMID:Wolff Award 1996. The actions of valproate and neurosteroids in a model of trigeminal pain. 899 May 96

This study evaluated the effects of spinal gamma-aminobutyric acid (GABA) receptor agonists on the tactile allodynia observed in rats with ligation of the L5/L6 nerve roots (Chung model) and chronic lumbar intrathecal catheters. In these rats, the spinal injection of the GABAB agonist baclofen (BAC; 0.03-03 micrograms) and GABAA agonist muscimol (MUS; 0.1-1.0 micrograms) resulted in a dose-dependent antagonism of the allodynia at doses which had no detectable effect upon motor function. Intrathecal injection of the GABAB antagonist CGP 35348 (CGP; 30 micrograms) or the GABAA antagonist bicuculline (BIC; 0.3 micrograms) prior to injection of each GABA receptor agonist had little effect upon normal or tactile allodynic thresholds, but significantly reversed the anti-allodynic effects produced by the respective receptor agonists. The antagonistic effects were limited to the agonist of the respective receptor. These observations indicate that spinal GABAA and GABAB receptors modulate spinal systems activated by low threshold mechanoreceptors which mediate the allodynia observed following peripheral nerve injury.
Pain 1997 Mar
PMID:The effect of spinal GABA receptor agonists on tactile allodynia in a surgically-induced neuropathic pain model in the rat. 910 5

Activation of supraspinal gamma-aminobutyric acid-A (GABAA) receptors is known to result in antagonism of opioid analgesia. Since benzodiazepines enhance the action of GABA at GABAA receptors, we hypothesized that administration of these agents for preoperative sedation might antagonize the analgesic effects of opioids administered postoperatively. If so, then administration of the benzodiazepine antagonist flumazenil should enhance postoperative morphine analgesia. In a double-blind, placebo-controlled study of patients who received a preoperatively administered benzodiazepine (diazepam) for sedation and a postoperatively administered opioid (morphine) for analgesia, we investigated opioid-benzodiazepine interactions affecting postoperative dental pain. We found that flumazenil significantly enhanced morphine analgesia consistent with the hypothesis that the preoperatively administered benzodiazepine exerts an ongoing antianalgesic effect. In addition, we followed these patients over the first and second postoperative days to determine if there were differences between the drug groups in post-discharge pain, analgesic consumption, or side-effects. Participants receiving flumazenil reported significantly less post-discharge nausea and used significantly less ibuprofen. Since post-discharge pain levels were not significantly different, these results suggest that the patients receiving flumazenil required less analgesic medication to achieve a comparable level of pain control. In summary, our results indicate that the benzodiazepine antagonist flumazenil enhances morphine analgesia and decreases post-discharge side-effects as well as post-discharge need for analgesic medication.
Pain 1997 May
PMID:Benzodiazepine mediated antagonism of opioid analgesia. 920 Jan 70

Gabapentin, an anticonvulsant structurally related to gamma-aminobutyric acid (GABA) was recently reported to be effective in pain associated with reflex sympathetic dystrophy (RSD) and in pain associated with neuropathy. Yet, to our knowledge, the use of gabapentin for neuropathic pain in the presence of cognitive impairment has not been reported. In this report, we describe two patients (one with a traumatic brain injury, one with a putative acquired brain injury) who presented to a neurorehabilitation unit complaining of pain that was diagnosed as neurologically mediated. Within one week of receiving a daily 900 mg dose of gabapentin, both patients complained of heightened anxiety and restlessness. Correspondingly, each reported a diminution of psychological symptoms within 48 hours of gabapentin cessation. These two cases suggest that gabapentin may cause agitation in cognitive impaired patients. Physicians treating brain-injured patients and prescribing gabapentin for neuropathic pain may wish to closely monitor patients for similar signs of restlessness or anxiety.
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PMID:Psychomotor agitation following gabapentin use in brain injury. 921 Sep 89

This study investigated the role of gamma-aminobutyric acid (GABA) and GABA(A) receptors in the spinal cord in the expression of pain behaviors evoked by injection of formalin in concentrations ranging from 0.25 to 2.5% in the hindpaw of the rat. Two approaches were used. The first approach compared the effect of drug treatment to saline at each concentration of formalin. The second approach examined the effect of drug treatment on the concentration-response functions of formalin, i.e., its EC50. Intrathecal (i.t.) pretreatment with 0.03 to 0.3 microg of bicuculline, a GABA(A) receptor antagonist, dose-dependently increased the number of flinches and weighted pain scores in the interphase and phase 2, but did not alter responses in phase 1. In the interphase, the EC50 values of formalin for number of flinches or weighted pain score in bicuculline-pretreated rats were decreased to one-third or one-fourth, respectively, of their values in saline-pretreated rats. In phase 2, the EC50 values of formalin for number of flinches or weighted pain score in bicuculline-pretreated rats were similarly decreased to one-half of their value in saline-pretreated rats. These results suggest that formalin was a significantly more noxious stimulus in the presence of bicuculline. Pretreatment with the GABA(A) receptor agonists, muscimol (0.3 microg) or isoguvacine (10 or 30 microg i.t.), significantly decreased the number of flinches in phase 1 and phase 2, but produced only a marginal decrease in the weighted pain score at the highest doses. These findings suggest that there is little tonic activation of GABA(A) receptors by GABA in the spinal cord before or immediately after the injection of formalin. However, approximately 10 min after the induction of injury by formalin, there is a release of GABA and activation of GABA(A) receptors in the spinal cord that 1) contributes to the period of quiescence between phase 1 and phase 2 and 2) coincidentally diminishes the magnitude of pain behaviors in phase 2, possibly by limiting the development of central sensitization in the spinal cord.
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PMID:Role of spinal gamma-aminobutyric acidA receptors in formalin-induced nociception in the rat. 926 60

Increased pain fibre activity in response to tissue injury results in changes in gene expression, and prolonged changes in nerves and their environment. The resulting hyperalgesia and prolonged spontaneous pain are due both to increased sensitivity of peripheral nociceptors (primary hyperalgesia) and to facilitated spinal cord transmission (secondary hyperalgesia, receptive field expansion and allodynia). Hyperexcitability of dorsal horn neurones is first triggered by increased neuronal barrage into the central nervous system ('wind-up'), and later by retrograde chemical influences from the peripheral inflammation (central sensitisation). Central transmission and hyperexcitability are mediated by excitatory amino acids (aspartate and glutamate) and by tachykinins (substance P). Normally, the net effect of the activity in a complex network of inhibitory neurones in the spinal cord ('gate control'), driven by descending projections from brain stem sites, is to dampen and counteract the spinal cord hyperexcitability produced by tissue or nerve injury. Thus, peripherally evoked pain impulses pass through a filtering process involving gamma-aminobutyric acid, glycine and enkephalins. The activity of these substances in the spinal cord usually attenuates and limits the duration of pain. In the case of persistent pain, there is evidence of pathological reduction of the supraspinal net inhibitory actions in combination with ectopic afferent input in damaged nerves. Hence, the pathology of chronic pain (neuropathic pain) differs from that of nociceptive pain, and conventional pharmacological treatment of chronic central pain is usually less successful than treatment of inflammation-related pain. The many newly discovered mechanisms for the transmission and modulation of pain impulses are characterised by complex activity-dependent plasticity, which means that therapeutic strategies for persistent pain must be adapted to changing targets--either at the site of injury or at other sites in the central nervous system.
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PMID:[A breakthrough in the research on pain. Survey of the synaptic network may result in new analgesics]. 942 46


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