Parturition in the rat: a physiological pain model.

Background: Pain during labor is a common and severe phenomenon, but its clinical management remains haphazard because its neurophysiology is poorly understood. In the current study, the authors evaluate the parturient rat as a relevant model to study the pharmacology of labor pain.

Methods: Control of birth timing in term pregnant rats was achieved by gavage with RU 486 (5 mg/kg) the day before the expected day of parturition.

Effects of the high-efficacy 5-HT1A receptor agonist, F 13640 in the formalin pain model: a c-Fos study.

We studied the effects of the high-efficacy 5-hydroxytryptamine1A (5-HT1A) receptor agonist, F 13640 on both formalin-induced spinal cord c-Fos protein expression and pain behaviours in the rat. Replicating earlier data, F 13640 (0.63 mg/kg, i.

Morphine withdrawal precipitated by specific mu, delta or kappa opioid receptor antagonists: a c-Fos protein study in the rat central nervous system.

We have recently shown concurrent changes in behavioural responses and c-Fos protein expression in the central nervous system in both naive and morphine-dependent rats after systemic administration of the opioid antagonist naloxone. However, because naloxone acts on the three major types of opioid receptors, the present study aimed at determining, in the same animals, both changes in behaviour and c-Fos-like immunoreactivity after intravenous injection of selective opioid antagonists, such as mu (beta-funaltrexamine, 10 mg/kg), delta (naltrindole, 4 mg/kg) or kappa (nor-binaltorphimine, 5 mg/kg) opioid receptor antagonists, in naive or morphine-dependent rats. In a first experimental series, only beta-funaltrexamine increased c-Fos expression in the eight central nervous system structures examined, whereas no effect was seen after naltrindole or nor-binaltorphimine administration in naive rats.

The novel analgesic and high-efficacy 5-HT1A receptor agonist, F 13640 induces c-Fos protein expression in spinal cord dorsal horn neurons.

The very-high-efficacy, selective 5-HT(1A) receptor agonist, F 13640 produces uniquely powerful analgesia in rat models of chronic pain by novel neuroadaptive mechanisms (inverse tolerance and co-operation with nociception) [Neuropharmacology 43 (2002) 945-958]. A signal transduction theory and evidence suggest that F 13640 initiates these mechanisms, paradoxically, by mimicking the central effects of nociceptive stimulation. We report that the i.

Antinociceptive effects of RB101(S), a complete inhibitor of enkephalin-catabolizing enzymes, are enhanced by (+)-HA966, a functional NMDA receptor antagonist: a c-Fos study in the rat spinal cord.

The effects of the S enantiomer of RB101, a complete inhibitor of enkephalin-catabolizing enzymes, alone or in combination with a functional NMDA receptor antagonist, (+)-HA966 were studied on the spinal c-Fos protein expression in the carrageenan model of inflammatory nociception. One hour 30min after intraplantar carrageenan in awake rats, c-Fos immunoreactive (c-Fos-IR) nuclei were preferentially located in the laminae I-II and V-VI of the spinal dorsal horn, i.e.

Further evidence for the interaction of mu- and delta-opioid receptors in the antinociceptive effects of the dual inhibitor of enkephalin catabolism, RB101(S). A spinal c-Fos protein study in the rat under carrageenin inflammation.

We have previously shown that RB101, a dual inhibitor of enkephalin-degrading enzymes, decreased carrageenin-evoked c-Fos protein expression at the spinal cord level in awake rats. Moreover, we have also shown that c-Fos expression is a useful marker of the possible direct or indirect interactions between neural pathways, such as opioid and cholecystokinin systems. We now investigated the respective roles of the three main types of opioid receptors (mu, delta, or kappa) and their possible interactions, in the depressive effects of RB101 in inflammatory nociceptive conditions induced by intraplantar carrageenin (6 mg/150 microl of saline).

RB101(S), a dual inhibitor of enkephalinases does not induce antinociceptive tolerance, or cross-tolerance with morphine: a c-Fos study at the spinal level.

In behavioural tests, RB101 (N-[(S)-2-benzyl-3[(S)(2-amino-4-methyl-thio)butyldithio]-1-oxopropyl]-L-phenylalanine benzyl ester), a mixed inhibitor of enkephalin-degrading enzymes, induces antinociceptive effects without producing tolerance, or cross-tolerance with morphine. In the present experiments, the acute or chronic effects of enantiomer RB101(S) were examined on the response of spinal cord neurons to nociceptive inflammatory stimulation (intraplantar injection of carrageenin) using c-Fos studies in awake rats. The number of c-Fos immunoreactive nuclei was evaluated in the lumbar spinal cord 90 min after carrageenin.

Effects of nefopam on the spinal nociceptive processes: a c-Fos protein study in the rat.

We have evaluated the effects of nefopam on the spinal c-Fos protein expression in the model of acute (noxious heat) and persistent (intraplantar injection of formalin) nociception in the rat. One and two hours after i.pl.

Mu and delta opioid receptor-like immunoreactivity in the cervical spinal cord of the rat after dorsal rhizotomy or neonatal capsaicin: an analysis of pre- and postsynaptic receptor distributions.

Opioid compounds have powerful analgesic properties when administered to the spinal cord. These effects are exerted through mu and delta opioid receptors, and both pre- and postsynaptic mechanisms have been implicated. To specifically address the relative pre- and postsynaptic contribution to spinal opioid analgesia, we have quantitatively assessed the pre- vs.

Increased nitric oxide release by transient peripheral noxious inputs to the spinal cord of rats: an in vivo voltammetric approach.

Using in vivo voltammetric detection of nitric oxide (NO) a previous study demonstrated an increased NO release at the lumbar dorsal horn level of the spinal cord by peripheral inflammatory processes in decerebrated-spinalized rats. This study concerns the effects of acute peripheral stimulations. Gentle non-noxious or isolated nociceptive stimulation did not modify the oxidation current due to NO.

Intravenous morphine does not modify dorsal horn touch-evoked allodynia in the mononeuropathic rat: a Fos study.

In a model of mononeuropathic pain (chronic constriction injury of the sciatic nerve, CCI), we have demonstrated that light touch stimuli (stroking) to the paw induced Fos-like immunoreactivity (Fos-LI) in the superficial and deep dorsal horn of the rat spinal cord (Catheline et al., Pain 80 (1999a) 347). The efficacy of opioids in neuropathic pain being controversial, we have tested the effects of morphine (0.

Enhanced effects of co-administered dexamethasone and diclofenac on inflammatory pain processing and associated spinal c-Fos expression in the rat.

This study determines the effects of dexamethasone versus co-administered dexamethasone and diclofenac, on carrageenan-evoked spinal c-Fos expression and peripheral oedema in the freely moving rat. Drugs were administered intravenously 25 min before intraplantar injection of carrageenan (6 mg/150 microliters of saline). Three hours later the number of spinal c-Fos-LI neurones and peripheral oedema were assessed.

Aspirin and acetaminophen reduced both Fos expression in rat lumbar spinal cord and inflammatory signs produced by carrageenin inflammation.

This study, performed in freely moving rats, evaluates the effects of the two most prescribed analgesics, aspirin and acetaminophen, on carrageenin inflammation and the associated c-Fos expression in the rat lumbar spinal cord. Maximal dorsal horn c-Fos expression is observed 3 h after carrageenin (6 mg/150 microliters of saline), with Fos-like (Fos-LI) neurones being predominantly located in laminae I-II and V-VI (41 +/- 3% and 39 +/- 5% of the total number of Fos-LI neurones per section for the control group, respectively) of the dorsal horn. Pretreatment with aspirin (75 or 150 mg/kg, i.

Chronic treatments with aspirin or acetaminophen reduce both the development of polyarthritis and Fos-like immunoreactivity in rat lumbar spinal cord.

We have previously shown that during the development of adjuvant-induced arthritis (AIA), and without any peripheral stimulation, the number of Fos-like immunoreactive (Fos-LI) neurons in lumbar spinal cord increases in parallel with the clinical and behavioral signs of the disease and peaks 3 weeks after the inoculation which corresponds to the maximal stage of hyperalgesia (Abbadie and Besson 1992a). The aim of this study was to evaluate the suitability of the Fos-LI technique to gauge the effects of the two most prescribed analgesics, aspirin and acetaminophen (paracetamol), on spinal cord neurons of polyarthritic rats. The effects of the two drugs were tested on the "evoked" Fos-LI induced by peripheral mechanical noxious stimulus, as well as the effects of a chronic treatment on "basal" Fos-LI appearing during the development of polyarthritis in the absence of any intentional stimulation.

Effects of morphine and naloxone on basal and evoked Fos-like immunoreactivity in lumbar spinal cord neurons of arthritic rats.

We have previously shown, on the one hand, that the number of Fos-like immunoreactive (Fos-LI) neurons in the lumbar spinal cord observed during the development of adjuvant-induced arthritis in the rat correlates with the clinical and behavioral scores and, on the other hand, that the number of Fos-LI neurons induced by repeated mechanical pressure to the ankle was greater in arthritic animals than in healthy ones. In non-stimulated arthritic rats, Fos-LI neurons were mainly present in the neck of the dorsal horn and in the ventral horn of L3-L5, whereas following stimulation they were numerous in the superficial laminae. The aim of this study was to evaluate Fos-LI following morphine injection (1) in arthritic animals in the absence of any stimulation, (2) in arthritic rats after ankle stimulation pretreated with morphine or by the combination of morphine and naloxone, and (3) following naloxone treatment in non-stimulated and stimulated polyarthritic rats.

Chronic pain induces a paradoxical increase in growth hormone secretion without affecting other hormones related to acute stress in the rat.

In several diseases chronic pain is associated with long-lasting pathophysiological responses which differ strongly from those observed in acute situations. When persisting, acute pain often results in physical and psychological stress which may in turn aggravate the initial pathological state. In the present work we examined the secretory patterns of pituitary hormones related to acute stress (growth hormone (GH), prolactin (PRL) and beta-endorphin (beta-END)) in rats during the phase of Freund adjuvant-induced arthritis (AIA, a model used for chronic pain studies) when chronic pain is maximum (14 and 21 days, postinoculation (PI)).

A limited arthritic model for chronic pain studies in the rat.

Freund's adjuvant induced polyarthritis in rats has been used extensively to study pain processes of long duration. There are limitations of this model for chronic studies of pain/arthritis since the severe systemic changes provoke ethical concerns and also affect behaviour, physiology and biochemistry. Attempts to limit adjuvant-induced arthritis by plantar injection of the inoculum have been made.

Benzodiazepines and pain: effects of midazolam on the activities of nociceptive non-specific dorsal horn neurons in the rat spinal cord.

The high density of GABA-benzodiazepine receptors in the superficial dorsal horn suggests a possible involvement of benzodiazepines (BZs) in the modulation of spinal pain processes. In this electrophysiological study we have examined the effects of midazolam (MZ), a water-soluble short-acting BZ, on the activities of 57 nociceptive non-specific dorsal horn cells, one in each animal. Recordings were performed at lumbar level in unanesthetized decerebrate spinal rats before and following intravenous injection of MZ (1, 2 or 5 mg/kg).

Attempts to gauge the relative importance of pre- and postsynaptic effects of morphine on the transmission of noxious messages in the dorsal horn of the rat spinal cord.

Both pre- and postsynaptic mechanisms have been proposed as an explanation of the depressive effects of opioids on the activity of nociceptive dorsal horn neurons. In order to gauge the importance of the two mechanisms, we studied the effect of morphine on the spontaneous hyperactivity of nociceptive dorsal horn neurons in the spinalized decerebrated deafferented rat (C5-Th1). In this preparation, intravenous morphine was shown to depress spontaneous firing rate in a dose-dependent fashion.

Complex temporal changes in 5-hydroxytryptamine synthesis in the central nervous system induced by experimental polyarthritis in the rat.

The purpose of this study was to investigate modifications of 5-HT synthesis in a chronic pain model, the arthritic rat, at different times after the inoculation with Freund's adjuvant. This study confirms our previous findings that experimental induced polyarthritis is associated with a marked increase in free tryptophan levels in serum. During the acute phase of the disease (15-21 days after the adjuvant), the general increase in 5-HT synthesis observed in the CNS appeared to be related to an increase in tryptophan availability due to the elevation of free tryptophan in serum.

Do acute or chronic tricyclic antidepressants modify morphine antinociception in arthritic rats?

In a chronic pain model, the arthritic rat, tricyclic antidepressants (TCAs) have been shown to clearly reduce behavioural signs of nociception. In the present work, using a test of acute nociception (vocalization threshold to graded foot pressure) in the same model, we evaluated the possible potentiation of morphine analgesia by 2 TCAs: amitriptyline (AMIT) and imipramine (IMIP). Using this test of acute nociception, we failed to demonstrate any analgesic effect of AMIT or IMIP given either acutely or chronically.

Reduction of arthritis and pain behaviour following chronic administration of amitriptyline or imipramine in rats with adjuvant-induced arthritis.

Tricyclic antidepressants (TCAs) are used extensively to treat chronic pain in man without an adequate explanation for their activity. The purpose of the present study was to investigate this problem by testing the effect of chronic TCAs in an animal pain model: the arthritic rat. Sprague-Dawley rats with adjuvant-induced arthritis were injected daily for 4 weeks with amitriptyline (10 mg/kg) or imipramine (10 mg/kg) or saline, beginning 21 days after the induction of arthritis.

Electrophysiological characteristics of dorsal horn cells in rats with cutaneous inflammation resulting from chronic arthritis.

(1) Electrophysiological properties of dorsal horn neurones have been investigated in decerebrate, immobilized spinal rats rendered polyarthritic by intradermal injection of Freund's adjuvant. Since arthritis is associated with pronounced erythema and oedema of the foot sole and ankle areas, this particular study was devoted to the induced modifications of responses of units driven by cutaneous inputs. It allowed comparison with previous studies performed in healthy animals.

Total and free serum tryptophan levels and brain 5-hydroxytryptamine metabolism in arthritic rats.

In rats suffering from experimentally induced arthritis produced by Freund's adjuvant, there is a marked decrease in total serum tryptophan levels and a marked increase in plasma-free tryptophan levels at both 15 and 21 days after the administration of the adjuvant. Tryptophan, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid levels are increased in the brain and the spinal cord at 15 days. However, 21 days after administration of the adjuvant these levels returned to normal values in the brain, but remained increased in the spinal cord.

Diffuse noxious inhibitory controls (DNIC). II. Lack of effect on non-convergent neurones, supraspinal involvement and theoretical implications.

(1) Diffuse noxious inhibitory controls (DNIC) were tested for their effect on noxious only, non-noxious and proprioceptive cells in the dorsal horn of the intact anaesthetized rat. Unlike convergent neurones, as described in the previous paper, there was no effect of DNIC on these neurones. It is concluded that convergent neurones are specifically inhibited by DNIC.