Lumbar facet joint compressive injury induces lasting changes in local structure, nociceptive scores, and inflammatory mediators in a novel rat model.

Objective. To develop a novel animal model of persisting lumbar facet joint pain. Methods.

Neuropathic pain as a process: reversal of chronification in an animal model.

Peripheral neuropathic pain arises from trauma to sensory nerves. Other types of acute neurotrauma such as stroke and spinal cord injury are treated immediately, largely to prevent secondary damage. To pursue the possibility that neuropathic pain may also be amenable to early treatment, a rat model of neuropathic pain was induced using a 2-mm polyethylene cuff implanted around one sciatic nerve.

Characterization of a rat model of metastatic prostate cancer bone pain.

Purpose: The objectives of this study were to establish and characterize a novel animal model of metastatic prostate cancer-induced bone pain.

Methods: Copenhagen rats were injected with 10(6) MATLyLu (MLL) prostate cancer cells or phosphate-buffered saline by per cutaneous intra femoral injections into the right hind leg distal epiphysis. Over 13 days, rats progressively developed a tumor within the distal femoral epiphysis.

Sensory and vascular changes in a rat monoarthritis model: prophylactic and therapeutic effects of meloxicam.

Objective And Design: The objective of this study was to determine the ability of meloxicam prophylaxis and therapy to blunt the effect of complete Freund's adjuvant (CFA) induced monoarthritis.

Materials And Methods: First the validity of this animal model was established by examining joint changes at multiple levels after injecting CFA into the tibio-tarsal joint. Next, meloxicam (5 mg/kg) or vehicle was administered on days 0-7 (prophylactic) and on days 7-16 (therapeutic) in separate groups of animals.

Physiological evidence of a postsynaptic inhibition of the tail flick reflex by a cannabinoid receptor agonist.

Current evidence indicates that cannabinoids are antinociceptive and this effect is in part mediated by spinal mechanisms. Anatomical studies have localized cannabinoid CB(1) receptors to pre- and postsynaptic sites within the spinal cord. However, behavioural tests have not clearly indicated the relative importance of each of these sites.

Central poststroke pain: an abstruse outcome.

Central poststroke pain (CPSP), formerly known as thalamic pain syndrome of Déjerine and Roussy, is a central neuropathic pain occurring in patients affected by stroke. It is one manifestation of central pain, which is broadly defined as central neuropathic pain caused by lesions or dysfunction in the central nervous system. Thalamic pain was first described 100 years ago by Déjerine and Roussy and has been described as "among the most spectacular, distressing, and intractable of pain syndromes".

Sensory neuron and substance P involvement in symptoms of a zymosan-induced rat model of acute bowel inflammation.

Intestinal inflammation is a painful syndrome with multiple symptoms, including chronic pain. This study examined the possible role of sensory neurons and substance P in symptoms of an animal model of acute intestinal inflammation. The model was induced by injecting ethanol and zymosan into the colon of anesthetized male rats.

Increased stress-induced analgesia in mice lacking the proneuropeptide convertase PC2.

Many neuropeptides involved in pain perception are generated by endoproteolytic cleavages of their precursor proteins by the proprotein convertases PC1 and PC2. To investigate the role of PC2 in nociception and analgesia, we tested wild-type and PC2-null mice for their responses to mechanical and thermal nociceptive stimuli, before and after a short swim in cold or warm water. Basal responses and responses after a cold swim were similar between the two groups.

Antidepressant-like effects of neurokinin receptor antagonists in the forced swim test in the rat.

Although a wide assortment of agents is currently available for the treatment of depression, this disorder remains poorly managed in a large proportion of patients. Traditional antidepressant treatments target the biogenic amine systems. However, a growing body of evidence is implicating the involvement of neuropeptides in depression, especially the neurokinin substance P.

Alterations in brain metabolism induced by chronic morphine treatment: NMR studies in rat CNS.

High-resolution (500 MHz) multiresonance/multinuclear proton (1H) nuclear magnetic resonance (NMR) spectroscopy was used to detect metabolic changes and cellular injury in the rat brain stem and spinal cord following chronic morphine treatment. Compensatory changes were observed in glycine, glutamate, and inositols in the brain stem, but not the spinal cord, of chronic morphine-treated rats. In spinal cord, increases were detected in lactate and N-acetyl-aspartate (NAA), suggesting that there is anaerobic glycolysis, plasma membrane damage, and altered pH preferentially in the spinal cord of chronic morphine-treated rats.

Differential effects of NMDA and group I mGluR antagonists on both nociception and spinal cord protein kinase C translocation in the formalin test and a model of neuropathic pain in rats.

Coincident with nociception, both noxious chemical stimulation of the hind paw and chronic constriction injury (CCI) of the sciatic nerve produce an increase in protein kinase C (PKC) translocation in the spinal cord of rats. Noxious stimulus-induced PKC translocation likely depends on glutamate activity at either N-methyl-D-aspartate (NMDA) receptors or group I metabotropic glutamate receptors (mGluR1/5) in the spinal cord dorsal horn. This study compares nociceptive responses to, and the alterations in membrane-associated PKC, induced by noxious chemical stimulation of the hindpaw and CCI of the sciatic nerve, as well as their modulation by both NMDA and mGluR1/5 receptor antagonists.

Knockdown of spinal metabotropic glutamate receptor 1 (mGluR(1)) alleviates pain and restores opioid efficacy after nerve injury in rats.

1. Nerve injury often produces long-lasting spontaneous pain, hyperalgesia and allodynia that are refractory to treatment, being only partially relieved by clinical analgesics, and often insensitive to morphine. With the aim of assessing its therapeutic potential, we examined the effect of antisense oligonucleotide knockdown of spinal metabotropic glutamate receptor 1 (mGluR(1)) in neuropathic rats.

Influence of formalin concentration on the antinociceptive effects of anti-inflammatory drugs in the formalin test in rats: separate mechanisms underlying the nociceptive effects of low- and high-concentration formalin.

The present study has assessed the relationship between formalin-induced nociception and formalin-induced inflammation by comparing the dose-related effects of anti-inflammatory treatments on both nociceptive scores and plasma extravasation in the rat hind paw in response to high and low concentrations of formalin. The degree of plasma extravasation produced by 1% formalin did not differ significantly from that produced by the same volume of saline, and was not significantly affected by either of the anti-inflammatory agents. The 5% formalin injection produced significant plasma extravasation that was dose-dependently reduced by both dexamethasone and ibuprofen.

Physiological evidence that the 'interphase' in the formalin test is due to active inhibition.

Injection of a dilute solution of formalin into a rat hindpaw produces a biphasic nociceptive response consisting of an early phase during the first 5 min after formalin injection and a later phase starting after 15 min and lasting for 40-50 min. The period between the two phases of nociceptive responding is generally considered to be a phase of inactivity. We compared the nociceptive behaviors produced by a single hindpaw injection of 50 microl of formalin with those produced by two formalin injections given 20 min apart.

Evidence for tonic activation of NK-1 receptors during the second phase of the formalin test in the Rat.

Behavioral, electrophysiological, and autoradiographic experiments were done to study the second nociceptive phase in the formalin test. In initial experiments, this second phase was attenuated by 1-10 mg of the NK-1 receptor antagonist CP-99,994, given subcutaneously 10, 30, or 60 min before formalin (n = 8-10) and by 20 microgram given intrathecally 20 min after formalin (n = 13); the inactive isomer CP-100,263 was ineffective. In electrophysiological experiments on single dorsal horn neurons in vivo, the excitatory responses to subcutaneous formalin injection (50 microliter, 2.

Comparison of the effects of treatment with intrathecal lidocaine given before and after formalin on both nociception and Fos expression in the spinal cord dorsal horn.

Background: It has been proposed that the measure of noxious stimulus-induced Fos (the protein product of the immediate early gene c-fos) expression in the spinal cord dorsal horn of laboratory animals may provide an estimate of the potential of specific treatments to produce preemptive analgesia. The present study examined this hypothesis by comparing the effects of intrathecal lidocaine given before and after hindpaw formalin injection on persistent nociceptive responses and Fos expression in spinal cord dorsal horn of rats.

Methods: Formalin-induced nociception and Fos expression in the spinal cord, in response to a 50-microl injection of 2.

Intense peripheral electrical stimulation evokes brief and persistent inhibition of the nociceptive tail withdrawal reflex in the rat.

In a study of modulation of nociception by sensory inputs, electrical stimulation was applied to specific sites in the hindlimb and effects on the nociceptive tail withdrawal reflex were monitored in the lightly anaesthetized rat. Stimulation was applied to previously defined sites in the hindlimb, meridian points femur-futu (ST-32), fengshi (GB-31) and zusanli (ST-36). It consisted of a 4 Hz train of 2 ms square pulses given for 20 min at 20 x the threshold intensity required for muscle twitch.

SR 48968 specifically depresses neurokinin A- vs. substance P-induced hyperalgesia in a nociceptive withdrawal reflex.

To determine the role of neurokinin A and tachykinin NK2 receptors in processing of nociceptive information at the spinal level, the selective NK2 receptor antagonist, SR 48968 (S)-N-methyl-N [4-(4-acetylamino-4-[phenyl piperidino)-2-(3,4-dichlorophenyl)-butyl] benzamide, was tested for its effects on the hyperalgesia produced in the tail flick reflex by intrathecal administration of neurokinin A and of substance P. SR 48968 was also tested in a model in which noxious peripheral stimulation has been shown to produce hyperalgesia via a substance P mechanism. SR 48968 given intrathecally had a dose-dependent inhibitory effect on both the behaviour and the hyperalgesia induced by neurokinin A but not on either of these effects produced by substance P.

Effects of preemptive or postinjury intrathecal local anesthesia on persistent nociceptive responses in rats. Confounding influences of peripheral inflammation and the general anesthetic regimen.

Background: Although experimental evidence indicates that preemptive intrathecal treatment with local anesthetics reduces postinjury neuronal hyperexcitability, clinical evidence indicates that preemptive treatments do not consistently reduce postoperative pain. The current study used experimental models of postinjury nociception, in which rats received subcutaneous or intraarticular injections of the irritant formalin, to evaluate the effects of peripheral inflammation, or the use of agents supplemental to anesthesia, as possible confounding influences on the effectiveness of preinjury and postinjury intrathecal local anesthetic treatments.

Methods: In experiment 1, lumbar intrathecal lidocaine (30 microliters, 2%), given either 5 min before or 5 min after hind paw injection of 50 microliters of varying concentrations of formalin, was compared with intrathecal cerebrospinal fluid, for their effects on nociceptive responses in the late phase of the formalin test.

Implication of a nitric oxide synthase mechanism in the action of substance P: L-NAME blocks thermal hyperalgesia induced by endogenous and exogenous substance P in the rat.

The effects of i.p. administration of the nitric oxide synthase inhibitor NG-nitro-L-arginine methylester (L-NAME) and its inactive isomer, D-NAME, were tested in two nociceptive paradigms in the rat.

mu-, delta- and kappa-opiate receptors mediate antinociception in the rat tail flick test following noxious thermal stimulation of one hindpaw.

Experiments were performed to investigate the possible involvement of spinal mu-, delta- and kappa-opiate receptors in mediating the antinociceptive effects of noxious thermal stimulation of one hindpaw on the tail flick reflex in the rat. Male Sprague-Dawley rats were implanted with chronic intrathecal catheters to the lumbar level of the spinal cord. After 5 to 7 days, they were lightly anesthetized with an i.

Noxious thermal and chemical stimulation induce increases in 3H-phorbol 12,13-dibutyrate binding in spinal cord dorsal horn as well as persistent pain and hyperalgesia, which is reduced by inhibition of protein kinase C.

We have previously suggested that protein kinase C (PKC) contributes to persistent pain in the formalin test. This study compared the effects of pharmacological inhibition of PKC with either GF 109203X or chelerythrine on persistent pain following noxious chemical stimulation with its effects on mechanical hyperalgesia, which develops in the hindpaw contralateral to an injury produced by noxious thermal stimulation. Furthermore, we have assessed changes in membrane-associated PKC in spinal cord in response to both noxious chemical and thermal stimulation.

Noxious peripheral stimulation produces antinociception mediated via substance P and opioid mechanisms in the rat tail-flick test.

Physiological experiments were run to examine the effects of noxious thermal stimulation of one hindpaw on the tail-flick reflex in the lightly anesthetized rat. Male Sprague-Dawley rats were anesthetized with an i.p.

Mechanisms underlying antinociception provoked by heterosegmental noxious stimulation in the rat tail-flick test.

Physiological studies were conducted to examine the effects of noxious stimulation of one hindpaw or one forepaw on the latency of the withdrawal reflex in the tail-flick test in lightly anesthetized spinally intact or transected rats. Male Sprague-Dawley rats were anesthetized with an intraperitoneal injection of a mixture of Na-pentobarbital (20 mg/kg) and chloral hydrate (120 mg/kg). After baseline readings were taken in the tail-flick test, the effects of various noxious stimuli applied to remote body regions were assessed.

Noxious stimulation decreases substance P binding in rat spinal dorsal horn: competition by endogenous ligand?

To determine the participation of NK-1 receptors in mediating inputs from noxious thermal stimulation, sustained noxious stimulation was applied to anaesthetized rats by immersing one hind paw in water for 1.5 min at different temperatures. After sacrificing the animal, lumbar spinal cords were removed and 20 microns sections were incubated with [125I]BH-substance P.