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

Peripheral nerve injury may lead to a chronic neuropathic pain state that results from an increase in excitability of central neurons. This central sensitization is mediated via an N-methyl-D-aspartic acid (NMDA) receptor and may involve the production of nitric oxide (NO). As NO is suggested to play a role in nociceptive transmission following nerve injury, we examined for altered NO synthase activity at multiple levels of peripheral and spinal neural tissue in a rat model of neuropathic pain. Peripheral neuropathy was induced in rats (N = 12) by ligation of the left L5 and L6 nerve roots. Six other rats had sham surgery. An ipsilateral decrease in paw withdrawal threshold to mechanical stimuli confirmed the presence of a neuropathic pain state. Samples of the lumbar and thoracic spinal cords, L4, L5, and L6 dorsal root ganglia (DRGs), and the sciatic nerves were obtained from the lesioned and contralateral sides at 2 and 4 weeks after neuropathic surgery (N = 6 per group). In the lumbar spinal cord, a bilateral decrease in nitric oxide synthase (NOS) activity was observed 2 and 4 weeks after neuropathic surgery. NOS activity was increased in the ipsilateral L5 and 6 DRGs 2 weeks following neuropathic surgery. An increase in NOS activity in the DRG may be an early mechanism for inducing more central changes. The bilaterally decreased NOS activity in the lumbar spinal cord may be secondary to a negative feedback mechanism resulting from increased NO production in the spinal dorsal root ganglia. Multiple alterations in expression of NOS activity that occur in both peripheral and central processing may play a role in the pain behavior resulting from peripheral nerve injury. (Preliminary results of these studies have been presented in abstract form at the annual meetings of the Society for Neuroscience, 1994, and the American Society of Anesthesiologists, 1994).
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PMID:Neuropathic pain in rats is associated with altered nitric oxide synthase activity in neural tissue. 879 Dec 33

Pain intensity was observed before and after the subcutaneous (s.c.) administration of ketamine hydrochloride (80 micrograms/kg/s.c.) or saline (0.9% NaCl given by the same route) in 17 migraine (M) sufferers as an acute treatment of their M attacks. The same parameter was observed in another group of 17 M-sufferers complaining of very severe and frequent M attacks; these subjects were completely refractory to the prophylactic treatments currently used in M. In this second group, ketamine 80 micrograms/kg/s.c./three times a day) or saline was randomly assigned in a short (3-week) chronic treatment. A randomized, double-blind, cross-over study design was used both when testing ketamine as an acute administration for relieving M attack and when comparing its effect to that of the placebo in a chronic treatment for preventing M-pain. Ketamine, but not placebo, produced a marked relief of pain both as an acute treatment and as a prophylactic therapy. Mild specific side-effects were observed in the majority of the patients treated with ketamine. Moreover in the placebo group, the majority of these patients also complained of side-effects. The present results support the hypothesis that N-methyl-D-aspartic acid (NMDA) receptors play an important role in the mechanisms of M.
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PMID:Exploration of NMDA receptors in migraine: therapeutic and theoretic implications. 883 16

The action of lignocaine on nociceptive transmission in the spinal cord has been studied in vitro using ventral root potential (VRP) recordings from 10-12-day-old rat hemisected spinal cord preparations. Single-shock stimulation of a dorsal root at intensities sufficient to activate high-threshold C-primary afferent fibres elicited VRPs lasting for 15-20 sec in the corresponding ventral root. The VRP consisted of 3 distinct parts: the early, slow and prolonged components, as previously described (Thompson et al. 1992), where the early represents A beta fibre-evoked mono- and polysynaptic responses lasting for tens of milliseconds, the slow is a largely N-methyl-D-aspartic acid (NMDA) receptor-mediated small-calibre afferent-generated component, lasting for about 1.5 sec, and the prolonged is a neurokinin receptor-mediated long-lasting component generated by high-threshold fibres. Lignocaine superfusion (40-60 microM) significantly and reversibly reduced the slow and prolonged components of the C fibre-evoked VRP in a dose-dependent manner without any effect on the early or A beta fibre-mediated component of the VRP. The amplitude of the cumulative VRP generated by repetitive inputs (1 and 10 Hz) was also significantly reduced as was the depolarization produced by bath application of NMDA (100 microM) or substance P (SP, 1 microM) in the presence or absence of tetrodotoxin (TTX) (300 nM). At this dose range lignocaine had no effect on the compound action potential (CAP) elicited by stimulating the sciatic nerve and recorded on the dorsal root. The CAP was only significantly reduced with a 300 microM dose of lignocaine. Application of the opiate, glycine, GABAA and GABAB receptor antagonists, naloxone (1 microM), strychnine (100 microM), bicuculline (100 microM) and phaclofen (100 microM) did not alter the depressant effects of lignocaine on the VRP. Low concentrations of lignocaine have a selective action on nociceptive transmission in the spinal cord which is different and more potent than its local anaesthetic conduction blockade in the periphery. This includes a reduction of direct or synaptically driven NMDA- and NK receptor-mediated post-synaptic depolarizations indicating that this class of sodium channel blockers may be potentially useful as analgesic agents, possibly acting on TTX-resistant sodium ion channels.
Pain 1996 Jan
PMID:Lignocaine selectively reduces C fibre-evoked neuronal activity in rat spinal cord in vitro by decreasing N-methyl-D-aspartate and neurokinin receptor-mediated post-synaptic depolarizations; implications for the development of novel centrally acting analgesics. 886 47

Adherence of sickle erythrocytes to vascular endothelium likely initiates or participates in microvascular occlusion, leading to ischemic tissue and organ damage characteristic of sickle-cell pain episodes. In vitro, sickle-cell adherence to endothelium involves adhesive plasma proteins and integrin and nonintegrin receptors on sickle cells and endothelial cells. The involvement of arginine-glycine-aspartic acid (RGD) sequences in adhesive plasma proteins and integrin receptors suggests that RGD-containing peptides may inhibit sickle-cell/endothelial-cell adherence. In the present study, inhibition of plasma-mediated sickle-erythrocyte adherence to endothelium using conformationally constrained RGD-containing peptides was quantified in vitro under continuous flow at a shear stress of 1.0 dyn/cm2. Two conformationally constrained RGD peptides were investigated: 6Z (which has high affinity for alpha5beta1, alpha(V)beta3, and alpha(IIIb)beta3 integrin receptors), and TP9201 (which preferentially binds to alpha(IIb)beta3). Peptide 6Z at 50 microM inhibited plasma-mediated sickle-cell adherence to microvascular endothelium 70% when incubated with sickle red cells, and 63% when incubated with endothelium. Under similar conditions, peptide TP9201 inhibited plasma-mediated sickle-cell adherence up to 85% at concentrations from 250 to 500 microM TP9201. The inhibition of plasma-mediated adherence by conformationally constrained RGD peptides, but not by linear or circular constructs, suggests that the tertiary structure of the peptide containing the binding sequence is important. Inhibition of plasma-mediated sickle-cell adhesion with these peptides in vitro suggests that such conformationally constrained RGD peptides could provide therapeutic interventions in the course of the disease by inhibiting receptor-ligand interactions.
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PMID:Inhibition of plasma-mediated adherence of sickle erythrocytes to microvascular endothelium by conformationally constrained RGD-containing peptides. 889 33

Increased postoperative pain may be caused by central nervous system plasticity, which may be related to actions of N-methyl-D-aspartic acid (NMDA) receptors on neurons in the dorsal horn of the spinal cord. Opioids act mainly on presynaptic receptors and reduce neurotransmitter release, while ketamine antagonizes NMDA receptors and prevents wind-up and long-term potentiation. Thus, we postulated that central nervous system sensitization would be prevented more effectively by the preoperative use of these two drugs simultaneously, and the effect of preemptive analgesia would be demonstrated. Ketamine, 60 mg, and morphine, 2 mg, were injected epidurally through an indwelling catheter that was inserted at the T7-8 interspace in 60 ASA physical status class 1-2 patients. The drugs were injected before induction of anesthesia (Group 1; n = 30) or immediately after removal of a surgical specimen (Group 2; n = 30). An additional 2 mg of morphine was injected when the patients complained of resting pain. The analgesic effect was assessed by the time from first analgesic injection to second dose and the number of patients who needed supplemental injections. Complications were also noted. The duration of analgesia was longer (P < 0.01) in Group 1 (31.1 +/- 16.0 h) than in Group 2 (21.1 +/- 12.0 h), and the proportion of patients who needed supplemental injections was decreased (P < 0.05) in Group 1 (56.7%) compared with Group 2 (90.0%). The incidence of adverse effects was not different between the two groups. In conclusion, preoperative administration of morphine and ketamine is more effective in reducing postoperative pain than it is when given during the operation.
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PMID:Epidural morphine plus ketamine for upper abdominal surgery: improved analgesia from preincisional versus postincisional administration. 905 1

A 14-year-old male patient developed severe right limb pain after traumatic sciatic nerve injury. His pain was diagnosed as neuropathic pain (complex regional pain syndrome, type II). He did not respond to any conventional therapy for limb pain including non-steroidal antiinflammatory drugs, antidepressants, anticonvulsants, continuous epidural administration of local anesthetics and psychotherapy. Following continuous epidural administration of a very low dose of ketamine, an N-methyl-D-aspartic acid (NMDA) receptor antagonist, 25 microg/kg per h for 10 days, complete pain relief was obtained without any side-effects. There has been no recurrence of pain for 8 months after discontinuation of epidural ketamine. The symptoms related to dysfunction of the sympathetic nervous system still remained after complete pain relief. We discuss pain mechanisms, pain relief and the use of ketamine in this case.
Pain 1998 Apr
PMID:The NMDA-receptor antagonist ketamine abolishes neuropathic pain after epidural administration in a clinical case. 958 76

The objective of the present study was to evaluate the effects of EMD 61753 (asimadoline), a kappa-opioid receptor agonist with restricted access to the central nervous system, on postoperative pain in patients who underwent knee surgery and on nociceptive thresholds and inflammation in rats treated with Freund's complete adjuvant. Patients treated with EMD 61753 (10 mg p.o.) tended to report an increase in pain, as evaluated by a visual analog scale and by the time to the first request for and the total amount of supplemental analgesic medication. The global tolerability of EMD 61753 was assessed as significantly inferior to that of a placebo by the investigator. In rats, the bilateral intraplantar (i.pl.) injection of EMD 61753 (0.1-3.2 mg) resulted in dose-dependent antinociception in both inflamed and noninflamed paws, with a peak at 5 min after injection, as evaluated by the paw pressure method. However, at later time points (1 h-4 days), a significant decrease in the paw pressure threshold was observed, confirming its tendency toward a hyperalgesic action in humans. This was accompanied by an increase in paw volume and paw temperature, with a peak at 6 h after injection. EMD 61753 (1.6 mg)-induced analgesia was blocked by the peripheral opioid receptor antagonist naloxone methiodide (2.5-10 mg/kg s.c.) and by the kappa receptor antagonist nor-binaltorphimine (0.1 mg; i.pl.). In contrast, EMD 61753 (1.6 mg)-induced hyperalgesia and increases in paw volume and paw temperature were blocked neither by naloxone methiodide (10-40 mg/kg s.c.) nor by dizocilpine maleate (0.003-0.009 mg i.pl.), a N-methyl-D-aspartic acid receptor antagonist. These data show differentially mediated peripheral actions of EMD 61753: kappa-opioid receptor-induced analgesia and nonopioid, non-N-methyl-D-aspartic acid hyperalgesic and proinflammatory effects.
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PMID:Peripheral effects of the kappa-opioid agonist EMD 61753 on pain and inflammation in rats and humans. 1038 99

The N-methyl-D-aspartic acid (NMDA) receptor antagonist D, L-2-amino-5-phosphonopentanoic acid (AP5) caused a stronger inhibition of wind-up in single wide dynamic range (WDR) neurons after carrageenan inflammation compared with control neurons without inflammation in the receptive field. This indicates that even a short period (2.5 h) of inflammation induces changes in the function of NMDA receptors. The drug effect was also studied in separate control experiments with few wind-up inducing stimulus trains and little nociceptive input prior to baseline recordings. In these control experiments all evoked responses were reduced by the drug, but the wind-up was significantly increased. A wind-up increase after NMDA receptor antagonism has been reported in two previous studies. Thus, other mechanisms than NMDA receptor stimulation may be more important for the wind-up in not sensitized dorsal horn neurons. As for long-term potentiation, it seems that NMDA receptor antagonists have an increased effect after sensitization. Thus, sensitized and not sensitized dorsal horn neurons may respond differently to an NMDA receptor active drug. In rats nerve stimulation and halothane anaesthesia induced larger evoked responses to afferent stimulation than cutaneous stimulation and urethane anaesthesia, the AP5 effect was however similar.
Pain 1999 Dec
PMID:Dorsal horn NMDA receptor function is changed after peripheral inflammation. 1056 60

The present study was designed to characterize the possible roles of spinally located cholera toxin (CTX)- and pertussis toxin (PTX)-sensitive G-proteins in excitatory amino acids induced pain response. Intrathecal (i.t.) injection of glutamate (20 microg), N-methyl-D-aspartic acid (NMDA; 60 ng), alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA; 13 ng), and kainic acid (12 ng) showed pain response. Pretreatment with CTX (0.05 and 0.5 microg, i.t.) attenuated pain response induced by glutamate, NMDA, AMPA and kainic acid administered i.t. in a dose-dependent manner. On the other hand, i.t. pretreatment with PTX further increased the pain response induced by glutamate, NMDA, AMPA and kainic acid administered i.t., especially at the dose of 0.5 microg. Our results suggest that, at the spinal cord level, CTX- and PTX-sensitive G-proteins appear to play opposite roles in modulating the pain response induced by spinally administered. Furthermore, CTX- and PTX-sensitive G-proteins appear to modulate pain response induced by stimuli of both NMDA and non-NMDA glutamate receptors.
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PMID:Differential modulatory roles of cholera toxin and pertussis toxin in the regulation of pain responses induced by excitatory amino acids administered intrathecally in mice. 1083 21

Adjuvant analgesics are drugs that have weak or nonexistent analgesic action when administered alone but can enhance analgesic actions when coadministered with known analgesic agents. Such agents are often administered in cases of refractory pain. For some chronic pain syndromes, however, they may constitute a first-line approach. Because pain is such an individual experience, analgesic regimens may require several drugs at varying dosages to confer a comfortable state. Adjunctive therapies such as the tricyclic antidepressants, anticonvulsants, N-methyl-D-aspartic acid receptor antagonists and low-dose intravenous local anesthetics, to name a few, have proved to be efficacious in relieving certain types of pain, especially neuropathic and cancer pain. Their use in animals is increasing, with anecdotal reports of some success.
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PMID:Adjunctive analgesic therapy. 1093 26


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