Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antinociceptive activities of heterocyclic antidepressants (HCAs) were studied after intrathecal (i.t.) administration in mice. HCAs with selective norepinephrine reuptake blocking properties (noradrenergic HCAs), such as desipramine and protriptyline, produced different antinociceptive profiles from HCAs with selective serotonin reuptake blocking properties (serotonergic HCAs), such as fluoxetine and citalopram. Noradrenergic HCAs were antinociceptive in all of the three nociceptive tests employed in the present study, i.e., tail-flick (TF) test, i.t. substance P-induced behavioral (SPB) test and intradermal hypertonic saline-induced behavioral (HSB) test. Intrathecal noradrenergic HCAs potentiated systemic or i.t. morphine-induced antinociception in the TF test. Serotonergic HCAs were partially antinociceptive in the SPB and HSB test, but inactive in the TF test. Furthermore, serotonergic HCAs did not enhance the antinociception produced by systemic or intrathecal morphine. The present data suggest that the efficacy of HCAs in the control of chronic pain stems, at least partially, from their action in the spinal cord, their analgesic activities probably involve blockade of monoamine reuptake. and the spinal serotonergic system probably possesses a dual action in regard to spinal nociception, while the noradrenergic system does not.
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PMID:Analgesic properties of intrathecally administered heterocyclic antidepressants. 349 77

The paper reviews evidence that adjuvant arthritis in the rat is associated with chronic pain and discusses the time course and measurement of this putative pain. The available evidence is consistent with the view that arthritic rats suffer pain, but it appears difficult to formally establish the occurrence of chronic pain in animals. The data suggest the pain to be severe during weeks 2 and 3 and to persist during weeks 4 and 5 after inoculation. The continuing inflammation of joints likely results in movement-induced acutely elicited pains that may persist till about the 8th week. The severe pain during weeks 2 and 3 may be associated with a depression of some drives, and the entire week 2-8 period is likely associated with varying levels of chronic stress. Neurochemical and neurophysiological studies indicate that adjuvant arthritis profoundly influences several of the neurotransmission and neuroendocrine functions of brain and spinal cord; among the affected systems are substance P-ergic, serotonergic and endorphinergic systems. Adjuvant arthritis in the rat constitutes the only laboratory animal model of chronic pain that has been validated to a significant extent. It is suggested that the model be examined further and that additional animal models of chronic pain be developed.
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PMID:Evidence that adjuvant arthritis in the rat is associated with chronic pain. 354 55

In the awake restrained rat the intrathecal administration of substance P or the partial substance P homologue eledoisin-related peptide (ERP) reduced reaction time to a noxious radiant heat stimulus and, at high doses, produced additional behavioural responses suggesting that the animals had reacted to what they perceived as a painful stimulus. The reduction in tail-flick latency was observed as early as 30 sec following peptide administration peaked at 1 min and persisted for 5-10 min, after which an overshoot of the response (i.e., an increase in reaction time) was observed. The responses varied in their magnitude with the amount of peptide given, substance P being approximately 4 times more potent on a molar basis than ERP. Intrathecal administration of an equal volume of vehicle (artificial cerebrospinal fluid) had no effect on tail-flick latency and failed to produce any of the other behavioural changes. The following interpretations are made. The decrease in tail-flick latency suggests that pain threshold was decreased, and the dramatic behavioural effects seen at high doses suggest that an excess of substance P in the spinal cord is capable of producing a painful sensation. The rapid onset of the response suggests rapid penetration of substance P and ERP to the appropriate receptors, and the rapid decay of the response suggests rapid removal. Taken together, these results are consistent with the earlier suggestion that substance P plays a role as an excitatory agent in sensory pathways subserving pain. It is proposed that some conditions of chronic pain in man may therefore be due to an overabundant amount of substance P. This is complementary to a second proposal that other cases of chronic pain may be due to a supersensitivity of substance P receptors. The former is more likely to be associated with organic disorders, the latter with nerve damage, e.g. with causalgia, the neuralgias and perhaps some cases of phantom limb pain.
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PMID:Substance P reduces tail-flick latency: implications for chronic pain syndromes. 618 63

The study determined the effects of intrathecal injection of 50 micrograms of capsaicin on respiration in rats with adjuvant arthritis as well as in control animals. Whole body plethysmographic measurements of steady-state frequency, tidal volume, and minute volume of respiration were made 3 hours and for up to 11 days after intrathecal injection. Capsaicin increased minute volume within 3 hours of its intrathecal injection in control animals. Intrathecal capsaicin also reduced the respiratory response to adjuvant arthritis in the experimental animals; the latter effect was apparent 11 days after injection. This biphasic pattern of capsaicin effects is consistent with a possible role of substance P in the chronic pain which is presumably associated with adjuvant arthritis in the rat.
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PMID:Respiratory effects of intrathecal capsaicin in arthritic and non-arthritic rats. 620 7

The anti-nociceptive effects of three tricyclic anti-depressants (desipramine, protriptyline, fluoxetine) were evaluated in mice following intrathecal administration. Nociceptive behavior was produced by intrathecal administration of Substance P and measured for 60 seconds following subcutaneous and intrathecal administration of vehicle and increasing doses of the drugs being tested. Systemically administered protriptyline produced dose related antinociception in this paradigm. A similar effect was seen following systemic desipramine; while fluoxetine was inactive systemically. Both protriptyline and desipramine given intrathecally were antinociceptive while fluoxetine had a biphasic effect, being analgesic only at low doses. These results indicate that tricyclic antidepressants may produce analgesia at the spinal level in rodents. This action may be related to the therapeutic success of tricyclic antidepressants in chronic pain syndromes.
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PMID:Anti-nociceptive effect of tricyclic anti-depressants following intrathecal administration. 633 32

Interleukin-1 is known to exert pleiotropic effects in host defence mechanisms and in inflammation. Chronic pain, inflammation and interleukin-1 beta enhance the production of substance P. Recently, axonal transport of opiate receptors was found to increase in rat sciatic nerves in the model of Freund's adjuvant-induced arthritis. Here we show that a single intraplantar injection of interleukin-1 beta is able to enhance the axonal transport of mu and kappa opiate receptors and substance P. Indeed, their accumulation was markedly increased in the proximal part of ligated sciatic nerves, but only in the paw injected with interleukin-1. The time course revealed a delayed onset and, more importantly, a long-term increase lasting at least six days, which is in contrast with the short-term pyrogenic effect of interleukin-1. Pretreatment of rats with capsaicin or administration of dexamethasone completely prevented the interleukin-1 beta effect. The present results suggest that interleukin-1 beta may serve as a mediator to sensitize nociceptors in chronic inflammation and possibly in hyperalgesia through long-term changes in neuronal plasticity.
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PMID:Interleukin-1 beta induces long-term increase of axonally transported opiate receptors and substance P. 747 20

Parallel time courses of preclinical and behavioural pain-related parameters and levels of substance P-like immunoreactivity in plasma (plasma-SPLI) and cerebrospinal fluid (CSF-SPLI) were studied in 2 groups of rats injected with an arthritogenic solution (concentrated Freund adjuvant) over a 9-week post-infection (PI) period; 1 group was pretreated with saline (control) and 1 pretreated with diluted Freund adjuvant (immunized). In control rats all symptoms of adjuvant-induced arthritis (AIA) developed while in immunized rats AIA symptoms were significantly reduced or did not appear. A significant increase in plasma-SPLI was obvious as early as the 2nd week PI and remained at this level in both groups of animals until the end of the 9-week PI observation period, but with a significantly higher increase in control versus immunized group at all stages. In contrast, CSF-SPLI transiently peaked only in the control group at 3 weeks PI whereas CSF-SPLI values did not differ from one week to another in both groups of rats. These results suggest that successive injections of diluted Freund adjuvant impairs the development of chronic inflammation and pain in AIA in rats, as well as the transient increase in SP release in CSF at 3 weeks PI, but not the long-lasting increased SP release in plasma. Since there is a clear dissociation between our biochemical and preclinical and behavioral data, this study does not provide evidence for the role of substance P as a possible biologic marker of chronic pain either in plasma or in CSF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevaccination with diluted Freund adjuvant prevents the development of chronic pain and transient release of cerebrospinal fluid substance P in adjuvant-induced arthritis in rats. 752 93

Chronic pain and inflammation increase substance P in sensory fibres of peripheral nerves in which opiate receptors are known to undergo axonal transport. The aim of the present study was to evaluate a possible modulation of axonal transport of opiate receptors in peripheral nerves during inflammation. After intraplantar injection of Freund's adjuvant to rats, the accumulation of mu and kappa opiate receptors increased on both sides of ligature in sciatic nerves of the injected paw. The contralateral side was unaffected and may serve as control. When IL-1 beta was injected into rat paws, the axonal transport of opiate receptors was increased in a similar way. This suggests that IL-1 beta represents a major mediator to sensitize nociceptors during inflammation through a process requiring retrograde signals.
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PMID:IL-1 beta-like Freund's adjuvant enhances axonal transport of opiate receptors in sensory neurons. 752 8

Electric stimulation applied to the posterior surface of the spinal cord (SCS) is an established treatment in certain chronic pain syndromes resistant to conventional therapeutic procedures. Despite the clinical value of SCS, the mechanisms behind the efficacy of the method are largely unknown. Several neurotransmitters in the CNS (e.g. opioids, serotonin, noradrenaline, substance P, GABA), have been proposed to be involved in the pain-alleviating effect of SCS. However, as yet there is no evidence that these would be involved in the beneficial effects of SCS. We have studied neurotransmitter release, using microdialysis techniques, in the spinal dorsal horn and the periaqueductal grey substance (PAG) of the rat and the cat, induced by SCS applied with current parameters equivalent to those used clinically in man. Up to now dialysates have been assayed for GABA, serotonin and substance P with highly sensitive methods. Three groups of studies have been carried out: (1) dorsal horn microdialysis in rats under halothane anesthesia during acute SCS; (2) dorsal horn microdialysis in cats under barbiturate anesthesia or following decerebration, and (3) PAG microdialysis in awake, unrestrained rats with chronic SCS. In the dorsal horn studies, microdialysis probes of different sizes were implanted in the lower lumbar dorsal horns. In the PAG studies, rats had guide cannulas for microdialysis stereotactically inserted into the PAG. SCS was applied at a low thoracic level with 50 or 100 Hz; 0.2 ms and an intensity amounting to 2/3 of the motor threshold. The microdialysis probes were perfused with modified Ringer's solution. Fractions of the dialysate were collected at various intervals. GABA and serotonin were assayed by reverse-phase HPLC, while substance P was investigated using a highly sensitive radioimmunoassay. SCS induced a significant release of GABA in the dorsal horn, most marked in the fraction following the stimulation period. In the rats with PAG microdialysis, the GABA level decreased significantly following two stimulation periods, although transitional increases during SCS were noted in some animals. In the decerebrated cat, a significant release of serotonin in the dorsal horn was obtained with SCS, while the levels of the metabolite 5-HIAA were little influenced by stimulation. On the contrary, in the decerebrated preparation there was no release of substance P in the dorsal horn with SCS, although in the intact cat under barbiturate anesthesia a significant release was induced.4+ off
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PMID:Release of neurotransmitters in the CNS by spinal cord stimulation: survey of present state of knowledge and recent experimental studies. 753 60

1. Monoarthritis was induced in Lewis rats by interdermal injection in the left hind paw of a suspension of Mycobacterium tubercolusis in mineral oil (500 micrograms 100 microliters-1). Controls were injected with 100 microliters mineral oil. 2. Withdrawal latencies to thermal stimuli of the inflamed paw, the contralateral and both paws of control rats were measured at daily intervals after injection by the plantar test. 3. After detection of the pain threshold, rat spinal cords were removed and horizontal dorsal slices were mounted in a 3-compartment bath to measure electrically-evoked release of substance P-like immunoreactivity (SP-LI). 4. The inflamed paw of monoarthritic rats exhibited a lower pain threshold to thermal stimuli than the contralateral paw of the same animals and both paws of control rats. Inflamed paw hyperalgesia was maximal two days after injection, and declined gradually between 7 to 21 days with no evidence of excitability of withdrawal reflexes after 28 days. 5. During the 28 days study, monoarthritic rats gained less weight than control rats. 6. Electrical stimulation of the dorsal roots attached to rat isolated spinal cord slices induced a significant increase (174 +/- 18% of basal outflow which was 30.3 fmol 8 ml-1, n = 5) in SP-LI release. 7. One-week after induction of inflammation no differences in the amount of SP-LI released from the spinal cord of incomplete Freund's adjuvant-treated rats (IFA) and Freund's adjuvant-treated rats (CFA) were detected. Two weeks after, CFA spinal cord tended to release more SP-LI than IFA cords and, 21 days after injection, the spinal cord of CFA rats released significantly more peptide than IFA rats (17.8 +/- 2.8 fmol ml-1, n = 12 and 6.9 +/- 3.2 fmol ml-1, n = 9, respectively).8. Twenty-one days after treatment, the evoked release from monoarthritic rat spinal cords was increased by 263 + 42% (n = 3) in the presence of the GABAB receptor antagonist, CGP 36742 (100 micro M)which also significantly potentiated monoarthritis-induced hyperalgesia up to 45 min after injection(100 mgkg-1, i.p.).9. These findings may provide a basis for a novel approach to chronic pain therapy but also an explanation for the lack of analgesia produced by the GABAB agonist, baclofen, in chronic as compared to acute pain.
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PMID:Spinal cord SP release and hyperalgesia in monoarthritic rats: involvement of the GABAB receptor system. 753 91


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