Articles: hyperalgesia.
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Comparative Study
Visceral and somatic hypersensitivity in a subset of rats following TNBS-induced colitis.
Chronic abdominal pain is one of the most common gastrointestinal symptoms experienced by patients. Visceral hypersensitivity has been shown to be a biological marker in many patients with chronic visceral pain. We have previously shown that IBS patients with visceral hypersensitivity also have evidence of thermal hyperalgesia of the hand/foot. ⋯ Transient colonic inflammation leads to chronic visceral and somatic hypersensitivity in a subset of rats. These findings are similar to the subset of patients who develop chronic gastrointestinal symptoms following enteric infection.
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Anesthesia and analgesia · Jan 2008
The prolonged analgesic effect of epidural ropivacaine in a rat model of neuropathic pain.
In clinical practice, the analgesic effects of epidurally administered local anesthetics on chronic pain sometimes outlast the duration of drug action expected from their pharmacokinetics. To investigate the underlying mechanisms of this prolonged effect, we examined the effects of ropivacaine, a local anesthetic, on pain-related behavior in a rat model of neuropathic pain. We also analyzed changes in the expression of nerve growth factor (NGF), which is involved in plasticity of the nociceptive circuit after nerve injury. ⋯ Repetitive administration of ropivacaine into the epidural space in CCI rats exerts an analgesic effect, possibly by inducing a plastic change in the nociceptive circuit.
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J. Pharmacol. Exp. Ther. · Jan 2008
Intrathecal administration of proteinase-activated receptor-2 agonists produces hyperalgesia by exciting the cell bodies of primary sensory neurons.
Proteinase-activated receptors (PARs) are a family of G-protein-coupled receptors that are activated by endogenous serine proteinases that cleave the N-terminal domain of the receptor unmasking a "tethered ligand" sequence. Trypsin and other agonists at PAR(2) act on peripheral nerves to augment the transfer of nociceptive information. We tested whether PAR(2) agonists also exert a spinal pronociceptive effect by i.t. administering the selective ligand, Ser-Leu-Ile-Gly-Arg-Leu-NH(2) (SLI-GRL). ⋯ PAR(2)-like immunoreactivity was found in DRG but not in spinal dorsal horn. These results suggest that activation of DRG neuron cell bodies may account for the pronociceptive actions of i.t. applied PAR(2) agonists. They also imply that pathophysiological release of PAR(2)-activating proteases in the vicinity of DRG neurons may produce profound effects on nociceptive processing in vivo.
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Sensory abnormalities are a key feature of Complex Regional Pain Syndrome (CRPS). In order to characterise these changes in patients suffering from acute or chronic CRPS I, we used Quantitative Sensory Testing (QST) in comparison to an age and gender matched control group. ⋯ We propose three pathomechanisms of CRPS I, which follow a distinct time course: Thermal hyperalgesia, observed in acute CRPS, indicates an ongoing aseptic peripheral inflammation. Thermal hypoaesthesia, as detected in acute and chronic CRPS, signals a degeneration of A-delta and C-fibres, which further deteriorates in chronic CRPS. PHS in acute CRPS I indicates that both inflammation and degeneration are present, whilst in chronic CRPS I, the pathomechanism of degeneration dominates, signalled by the absence of PHS. The contralateral changes observed strongly suggest the involvement of the central nervous system.
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Randomized Controlled Trial
Antihyperalgesic and analgesic properties of the N-methyl-D-aspartate (NMDA) receptor antagonist neramexane in a human surrogate model of neurogenic hyperalgesia.
NMDA-receptors are a major target in the prevention and treatment of hyperalgesic pain states in neuropathic pain. However, previous studies revealed equivocal results depending on study design and efficacy parameters. We tested the analgesic (generalized reduction of generation and processing of nociceptive signalling) and anti-hyperalgesic (prevention of central sensitization) properties of the NMDA-receptor antagonist neramexane and the potassium channel opener flupirtine in the intradermal capsaicin injection model. ⋯ The results suggests that in a human surrogate model of neurogenic hyperalgesia a single low-dose of neramexane had a marked analgesic effect in the sensitized and in the non-sensitized state and thus may be a useful drug to treat the enhanced pain sensitivity in neuropathic pain patients. Its efficacy may be based on analgesia rather than anti-hyperalgesia or anti-windup. In contrast, flupirtine showed neither an analgesic nor an anti-hyperalgesic effect at a dose used for the treatment of postoperative pain.