Possible chemical contribution from chromic gut sutures produces disorders of pain sensation like those seen in man.

Recently, it has been reported that loosely constrictive chromic gut ligatures around the sciatic nerve produce behavioral evidence of neuropathic pain in rats. It has been shown that axonal swelling after ligation results in a constriction injury associated with a decrease in the number of both large-diameter myelinated and small-diameter unmyelinated axons, but the mechanism(s) producing spontaneous pain and thermal hyperalgesia remain largely unknown. The present study systematically evaluated potential mechanisms involved in development of the behavioral changes produced by chromic gut ligatures loosely tied around the sciatic nerve.

Acute mechanical hyperalgesia is produced by coactivation of AMPA and metabotropic glutamate receptors.

Several recent reports document that activation of the NMDA receptor is required for the development and maintenance of thermal hyperalgesia. In contrast, the receptor subtype(s) involved in mechanisms that underlie mechanical hyperalgesia are at present unknown. We report here that acute mechanical hyperalgesia in the rat is not produced by NMDA receptor agonists, but instead requires coactivation of ionotropic AMPA and metabotropic glutamate receptor subtypes.

Ethanol dose-dependently attenuates NMDA-mediated thermal hyperalgesia in the rat.

Recent observations using acute and persistent pain models have suggested that activation of the N-methyl-D-aspartate (NMDA) receptor is required for mechanisms that underly the development and maintenance of thermal hyperalgesia. The present results document that both NMDA-mediated thermal hyperalgesia produced after acute intrathecal NMDA administration and NMDA-mediated thermal hyperalgesia produced in a model of neuropathic pain are dose-dependently and reversibly attenuated by intrathecal administration of ethanol (0.5-1.

Vagal afferent stimulation-produced effects on nociception in capsaicin-treated rats.

1. The effects of electrical stimulation of cervical vagal afferent fibers on the nociceptive tail-flick (TF) reflex and responses of spinal dorsal horn neurons to noxious cutaneous stimulation were studied in adult rats treated as neonates with either capsaicin or vehicle. 2.

Characterization of responses of T2-T4 spinal cord neurons to esophageal distension in the rat.

1. Three hundred fifty neurons in the T2-T4 spinal segments of 38 intact, pentobarbital sodium-anesthetized, pancuronium-paralyzed male rats were examined for somatic receptive fields and responses to midthoracic esophageal distension (ED). Recordings were made at a depth of 0.

Nitric oxide (NO) and nociceptive processing in the spinal cord.

There is considerable evidence to implicate N-methyl-D-aspartate (NMDA) receptor activation in the mechanisms that underly thermal hyperalgesia in the spinal cord. As many of the effects of NMDA receptor activation appear to be ultimately mediated through production of nitric oxide (NO), recent reports have begun to define the role of NO in spinal nociceptive processing. From this evidence, it is likely that NO, produced in neurons in the spinal cord that contain NO synthase, like NMDA, plays a pivotal role in multisynaptic local circuit nociceptive processing in the spinal cord.

Silent ischemia: a hypothetical mechanism.

Ischemia of visceral organs, especially the heart, is often a painful and potentially life-threatening condition. However, in at least 75% of all cases myocardial ischemia may be "silent" (i.e.

Unilateral hindpaw inflammation produces a bilateral increase in NADPH-diaphorase histochemical staining in the rat lumbar spinal cord.

Tissue injury results in several changes in spinal cord neurons that contribute to hyperalgesia arising from the injured tissue. In models of unilateral hindpaw inflammation, changes in the neurochemistry and electrophysiology of dorsal horn neurons ipsilateral, and to a much lesser extent contralateral, to the inflamed paw have been reported. For example, the excitability of dorsal horn neurons increases, receptive field size increases, and the content of various proteins and neuropeptides in the dorsal horn (e.

Neonatal capsaicin treatment prevents the development of the thermal hyperalgesia produced in a model of neuropathic pain in the rat.

Loose ligation of the sciatic nerve with 4-0 chromic gut sutures in rats produces behavioral evidence of neuropathic pain. In the present experiments we examined the involvement of capsaicin-sensitive afferents in mediating the thermal hyperalgesia produced by this model. Male Sprague-Dawley rats, treated as neonates (within 48 h of birth) with capsaicin (50 mg/kg, s.

Nitric oxide mediates the thermal hyperalgesia produced in a model of neuropathic pain in the rat.

Recent evidence has shown that activation of the N-methyl-D-aspartate receptor mediates the thermal hyperalgesia produced in a model of neuropathic pain. As the acute nociceptive effects of N-methyl-D-aspartate have been reported to be mediated through production of nitric oxide and activation of soluble guanylate cyclase, these experiments were designed to determine whether the thermal hyperalgesia produced in a rat model of neuropathic pain is also mediated through the production of nitric oxide and activation of soluble guanylate cyclase. Loose ligation of the sciatic nerve with chromic gut sutures, but not bilateral sham rats, demonstrated evidence of a marked thermal hyperalgesia on day 3 post-surgery.

Age, strain and anesthetic dependent differences in the nociceptive responses produced by i.v. 5-HT in the rat.

The intravenous (i.v.) administration of serotonin (5-HT) to rats is a noxious visceral stimulus which produces distinct vagal afferent-mediated pseudaffective responses, a passive avoidance behavior, a vagal afferent-mediated inhibition of the tail-flick (TF) reflex and a complex cardiovascular response.

Vagal afferent-mediated inhibition of a nociceptive reflex by i.v. serotonin in the rat. II. Role of 5-HT receptor subtypes.

In the rat, intravenous (i.v.) serotonin (5-HT) is a noxious stimulus which produces distinct vagal afferent-mediated pseudoaffective responses, a passive avoidance behavior, a vagal afferent-mediated inhibition of the nociceptive tail-flick (TF) reflex and a complex triad of cardiovascular responses.

Inhibition of a cutaneous nociceptive reflex by a noxious visceral stimulus is mediated by spinal cholinergic and descending serotonergic systems in the rat.

The present study examined the spinal pathway and receptors that mediate nocigenic inhibition of the tail-flick (TF) reflex produced by conditioning colorectal distension (CRD). Conditioning CRD (80 mmHg; 30 s) inhibited the TF reflex in all rats studied (n = 29). In 19 rats where intensity-dependent effects of CRD were studied, conditioning CRD in 7 rats facilitated the TF reflex at lesser, non-noxious intensities (mean 7.

Fos-like proteins in the lumbosacral spinal cord following noxious and non-noxious colorectal distention in the rat.

The rat lumbosacral spinal cord was immunocytochemically stained for Fos-like immunoreactivity following repetitive colorectal distention (CRD) to 20, 40 or 80 mm Hg. Following all 3 distention pressures, Fos-like immunoreactive (Fos-ir) nuclei were observed primarily in laminae I-II, V-VII and X, although some labeled nuclei were observed in laminae III-IV. Eighty mm Hg CRD resulted in significantly more Fos-ir nuclei than 20 or 40 mm Hg CRD.

Characterization of descending facilitation and inhibition of spinal nociceptive transmission from the nuclei reticularis gigantocellularis and gigantocellularis pars alpha in the rat.

1. Descending influences produced by focal electrical stimulation in the nuclei reticularis gigantocellularis (NGC) and gigantocellularis pars alpha (NGC alpha) on spinal nociceptive transmission and the dorsoventral region of spinal white matter mediating stimulation-produced modulation were examined in pentobarbital sodium-anesthetized, paralyzed rats. Spinal units studied responded to mechanical stimuli and noxious heating (50 degrees C) of cutaneous receptive fields confined to the glabrous skin of the ipsilateral hind foot.

Vagal afferent modulation of nociception.

Chemical, electrical or physiological activation of cardiopulmonary vagal (cervical, thoracic or cardiac), diaphragmatic vagal (DVAG) or subdiaphragmatic vagal (SDVAG) afferents can result in either facilitation or inhibition of nociception in some species. In the rat, these effects depend upon vagal afferent input to the NTS and subsequent CNS relays, primarily in the NRM and ventral LC/SC, although specific relay nuclei vary as a function of the vagal challenge stimulus. Spinal pathways and neurotransmitters have been identified for vagally mediated effects on nociception and consistently implicate the involvement of descending 5-HT and noradrenergic systems, as well as intrinsic spinal opioid receptors.

Bradykinin modulation of a spinal nociceptive reflex in the rat.

Bradykinin (BK) is a potent algesic compound. Therefore, we hypothesized that BK, acting as a peripheral noxious stimulus, would attenuate or inhibit responses to another noxious stimulus. When administered intravenously (i.

Production of endogenous nitric oxide and activation of soluble guanylate cyclase are required for N-methyl-D-aspartate-produced facilitation of the nociceptive tail-flick reflex.

The intrathecal (i.t.) administration of either N-methyl-D-aspartate (NMDA, 10 fmol to 10 pmol) or L-arginine (1 pmol to 10 nmol), but not D-arginine (1 pmol to 10 nmol), produced a rapid, transient, dose-dependent facilitation (maximal response of 30.

Modulation of cortical evoked potentials by stimulation of nucleus raphe magnus in rats.

1. In pentobarbital sodium-anesthetized rats, we evaluated changes in cortical evoked potentials (EPs) associated with electrical and chemical stimulation of nucleus raphe magnus (NRM). A condition-test (C-T) paradigm was used.

Antinociceptive synergy between intrathecal morphine and lidocaine during visceral and somatic nociception in the rat.

Clinical investigations have suggested a synergistic interaction between the analgesic effects of intrathecal opioids and local anesthetics; however, basic pharmacologic evidence for this observation has not been reported. Therefore, the authors have used models of visceral and somatic nociception to quantify the interaction between intrathecal morphine and lidocaine in a crossover study of 24 rats in four equal groups. Combinations of morphine and lidocaine were administered separately, corresponding to time of peak effect for each drug.

A critical review of the afferent pathways and the potential chemical mediators involved in cardiac pain.

There is considerable evidence that on the anterior surface of the heart (which is usually supplied by the left anterior descending and the proximal part of the left circumflex coronary arteries), sympathetic efferent reflexes characterized by tachycardia and/or hypertension predominate following experimental or pathological perturbations. These cardiovascular reflexes are accompanied by an increase in presumed nociceptive afferent traffic and, in pathological condition, by pain. In these experiments, there is generally no effect of vagotomy on afferent nerve traffic, and lower cervical and upper thoracic sympathectomies help provide relief from angina.

The peripheral nociceptive actions of intravenously administered 5-HT in the rat requires dual activation of both 5-HT2 and 5-HT3 receptor subtypes.

In 16-week-old Sprague-Dawley rats lightly anesthetized with pentobarbital, 5-HT (3-96 micrograms/kg, i.v.; n = 6) produced distinct pseudaffective responses and a dose-dependent (slope = 17.