Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intrathecal injections of capsaicin (CAP) and 4 other homovanillic acid (HMV) derivatives related to the structure of CAP were carried out. Capsaicin, 1-nonenoylvanillylamide (NVA), HMV-dodecylamide (DCA) (but not HMV-cyclohexylamide (CHA) or HMV-hexadecylamide (HDC] reduced the spinal content of substance P (SP), as measured by radioimmunoassay (RIA), and increased the tail-flick latency. Similar injection of kainic acid and piperine reduced levels of SP but failed to affect the tail-flick latency. None of the agents used affected spinal levels of cholecystokinin (CCK) or vasoactive intestinal peptide (VIP) as measured by RIA. In experiments using in vivo superfusion of the rat spinal cord, CAP, DCA and NVA were found to stimulate release of SP. Capsaicin had no effect on the levels of CCK or VIP immunoreactivity in the spinal superfusate. A tachyphylaxis to the effect of CAP and DCA on spinal SP release was demonstrated. Pretreatment with either agent blocked the releasing effect of the second. Pretreatment with an inactive analogue (HDC) had no effect on the subsequent activity of CAP. Kainic acid and piperine did not induce release of SP from the spinal cord. The relative selectivity of spinally administered capsaicinoids with regard to their effects on the content and release of peptides known to be contained in primary afferents and the presence of a similar structure-activity relationship for depletion and release of SP, desensitization and antinociception suggest the presence of a specific receptor site associated with a specific population of primary afferents through which pain information may pass. Whether SP is an 'afferent pain transmitter' is not clear, but at the least, it appears to serve as a marker for a population of afferents acted upon by spinally administered capsaicinoids.
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PMID:Action of intrathecal capsaicin and its structural analogues on the content and release of spinal substance P: selectivity of action and relationship to analgesia. 620 19

With the development of specific antibodies to vasoactive peptides and application of immunohistochemistry and radioimmunoassay methods, knowledge of vascular innervation has grown rapidly. In the cerebral circulation, four possible neurotransmitters are present: norepinephrine, acetylcholine, vasoactive intestinal peptide (VIP), and substance P. There is a dense adrenergic innervation of cerebral arteries, but contractile responses to nerve stimulation or circulating catecholamines are relatively small both in vitro and in vivo. Recent studies using radioligand binding techniques indicate a lack of specific 3H-prazosin binding in cerebral arteries, in contrast to other vascular beds. Thus a lack of alpha1-adrenergic receptors in cerebral arteries may account for weak responsiveness to sympathetic stimulation. Both VIP and acetylcholine may be vasodilator neurotransmitters, but blockade of cholinergic responses does not alter neurogenic vasodilation. The lack of specific VIP antagonists hampers efforts to explore this system more fully. Substance P-containing nerves are affected by capsaicin, supporting the hypothesis that these are primary sensory afferents, perhaps mediating pain. Future work in this area may focus on defining the pathways of these nerves and exploring the role of co-transmitters and possible interactions between nerves. With this basic information, experiments can be designed to elucidate more clearly the functional roles these nerves play.
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PMID:Innervation of the cerebral vasculature. 621 1

Long-acting somatostatin analogue (SMS 201-995) inhibits serotonin, bradykinin, prostaglandins, substance P, and vasoactive intestinal peptide, which may be involved in migraine. We therefore decided to test the efficacy of SMS 201-995 in relieving the pain of acute migraine attacks. Headache relief was defined as a reduction in severity from grade 3 or 2 (severe or moderate) to 1 or 0 (mild or none). Patients experiencing migraine attacks were evaluated clinically. A double-blind parallel group trial was performed in which patients randomly received either a subcutaneous injection of placebo (saline) or SMS 201-995 (100 micrograms). SMS 201-995 was significantly more effective than placebo in reducing headache grade at 2 h (1.5 +/- 0.6 vs 2.2 +/- 0.7; p < 0.01), 4 h (1.5 +/- 0.6 vs 2.1 +/- 0.8; p < 0.05) and 6 h (0.8 +/- 0.9 vs 2.1 +/- 0.8; p < 0.001) after the initiation of treatment. By 6 h, apparent headache relief (reduction in severity from grade 3 or 2 to 1 or 0) was experienced in 76.5% of SMS 201-995 treated patients and 25% of the placebo-treated group. Headache relief was significantly better in patients taking SMS 201-995 (p < 0.02). Furthermore, none of the patients became pain-free (headache grade 0) on placebo, while significantly more patients (47%) were pain-free on SMS 201-995 at 6 h (p < 0.01). Headache improvement started significantly earlier in those patients treated with SMS 201-995 than with placebo. SMS 201-995 significantly improves the pain of migraine attacks, 2 h after the beginning of treatment. Additionally, we observed no side effects of SMS 201-995. We therefore conclude that a single dose of 100 micrograms given subcutaneously is an effective and well-tolerated agent for the treatment of migraine attacks.
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PMID:Treatment of migraine attacks with a long-acting somatostatin analogue (octreotide, SMS 201-995). 905 32

Partial nerve injury is more likely to cause neuropathic pain than complete nerve injury. We have compared the changes in neuropeptide expression in primary sensory neurons which follow complete and partial injuries to determine if these might be involved. Since more neurons are damaged by complete injury, we expected that complete sciatic nerve injury would simply cause greater increases in neuropeptide Y and vasoactive intestinal peptide than partial injury. We examined neuropeptide Y and vasoactive intestinal peptide immunoreactivities in L4 and L5 dorsal root ganglia, the dorsal horn of L4-L5 spinal cord, and the gracile nuclei of rats killed 14 days after unilateral complete sciatic nerve transection, partial sciatic nerve transection and chronic constriction injury of the sciatic nerves. In all three groups of rats, neuropeptide Y- and vasoactive intestinal peptide-immunoreactive neurons were increased in the ipsilateral L4 and L5 dorsal root ganglion when compared with the contralateral side. Most neuropeptide Y-immunoreactive neurons were of medium and large size, but a few were small. Neuropeptide Y-immunoreactive axonal fibers were increased from laminae I to IV, and vasoactive intestinal peptide-immunoreactive axonal fibers were increased in laminae I and II, of the ipsilateral dorsal horn of L4-L5 spinal cord. The increases of neuropeptide Y and vasoactive intestinal peptide immunoreactivities in the dorsal horn were similar among the three groups. However, only after constriction injury were some vasoactive intestinal peptide-immunoreactive neurons seen in the deeper laminae of the ipsilateral dorsal horn. Robust neuropeptide Y-immunoreactive axonal fibers and some neuropeptide Y-immunoreactive cells were seen in the ipsilateral gracile nuclei of all three groups of animals, but neuropeptide Y-immunoreactive cells were more prominent after constriction injury. Contrary to our expectations, partial and complete sciatic nerve injuries induced similar increases in neuropeptide Y and vasoactive intestinal peptide in lumbar dorsal root ganglion neurons and their central projections in the dorsal horn and the gracile nuclei two weeks after injury. Some neurons whose axons were spared by partial injury may also increase neuropeptide Y or vasoactive intestinal peptide expression. Altered neuropeptide release from these functional sensory neurons may play a role in neuropathic pain.
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PMID:Partial and complete sciatic nerve injuries induce similar increases of neuropeptide Y and vasoactive intestinal peptide immunoreactivities in primary sensory neurons and their central projections. 969 28

The mechanism mediating the chronic pain associated with lumbar disc degeneration may involve neurotransmitters elaborated by dorsal root ganglion (DRG). This hypothesis has been tested in an applicable rabbit model of disc degeneration. Twenty control male rabbits underwent a soft-tissue release; 20 experimental rabbits sustained a facetectomy and capsulotomy and received an acute torsional lumbar injury. The levels of calcitonin gene-related peptide, vasoactive intestinal peptide, and substance P were measured in the DRG, spinal cord, and disc at 10, 30, 60, and 90 days postoperatively. Torsional injury was associated with a statistically significant increase in most DRG and spinal cord neurotransmitter values after 60-90 days. These points in time marked the periods of maximum biomechanical instability and disc narrowing. Such data support concepts about the association between chronic lumbar spinal instability, disc degeneration, and pain.
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PMID:Torsional injury resulting in disc degeneration in the rabbit: II. Associative changes in dorsal root ganglion and spinal cord neurotransmitter production. 972 1

Evans blue accumulated in parotid glands of conscious rats in response to feeding (over 60 min), in the absence of atropine and adrenoceptor antagonists and in their presence, and after pretreatment with the sensory neurotoxin capsaicin. Stimulation of the auriculo-temporal nerve (40 Hz, 10 or 20 min), without and with the blockers, caused Evans blue to accumulate. A periglandular oedema also contained the dye. Administration (i.v.) of neurokinin A accumulated Evans blue, while substance P, vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating peptide (PACAP), calcitonin gene-related peptide (CGRP) and pilocarpine lacked effect. Pilocarpine enhanced the action of neurokinin A and, furthermore, substance P combined with either VIP, PACAP or CGRP resulted in accumulation of Evans blue. In the sublingual + submandibular glands, Evans blue increased in response to neurokinin A and pilocarpine; furthermore, substance P and VIP, and substance P and CGRP, interacted positively. Bradykinin lacked effect in the glands. Comparisons were made with the urinary bladder. Accumulation of Evans blue reflects plasma protein extravasation. In salivary glands, the phenomenon occurred during feeding and was independent on intact sensory innervation; instead, the parasympathetic innervation containing the neuropeptides was in focus. In the clinic, the present findings may have implications for the aetiology of gland swelling and pain.
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PMID:Vascular protein leakage in the rat parotid gland elicited by reflex stimulation, parasympathetic nerve stimulation and administration of neuropeptides. 980 4

Itching reflects a distinct quality of cutaneous nociception elicited by chemical or other stimuli to neuronal receptors at the superficial layers of the skin and muco-cutaneous orifices. Although recent experimental studies of the conduction and perception of itch have yielded deeper insight into the physiology of this sensory quality, little is known about the neuromechanisms involved in pruritus accompanying many inflammatory skin diseases, in particular, in atopic eczema. Previous case-control studies of our research group with patients suffering from atopic eczema (AE) revealed significantly diminished itch perception after iontophoretic application of different doses of histamine as well as substance P (i.c. injected). Further experiments using acetylcholine (ACh, i.c.) clearly demonstrated that ACh elicits pruritus instead of pain in patients with AE. The first part of the present review deals with the results of our most recent case-control studies on histamine-induced itch perception in atopics devoid of eczema as well as in patients with urticaria or psoriasis compared to atopics with or without manifest eczema. We demonstrated that both focal itch and perifocal alloknesis (i.e., itch elicited by a slight mechanical, otherwise non-itching stimulus) were significantly reduced in eczema-free atopics yet were normal in non-atopics suffering from urticaria or psoriasis. In further studies using ACh i.c. injected into the uninvolved skin of patients with AE, lichen ruber, psoriasis, type IV contact eczema, or non-specific nummular eczema (n = 10/each group), all the atopics and 6/10 psoriatics felt itch instead of burning pain, but none of the others did. Different doses of vasoactive intestinal peptide (VIP) i.c. applied to the controls and the atopics with or without eczema did not markedly increase the intensity of nociceptive sensations. However, ACh induced pain in the controls, pure pruritus in the atopics with acute eczema, and a 'mixture' of pain and itch in the atopics just free from eczema. Obviously, the quality of sensations evoked by ACh and VIP depends on the inflammatory or non-inflammatory state of the atopic skin. In a placebo-controlled, double blind study on histamine-induced focal itch and alloknesis with healthy subjects (n = 15) using naltrexone (opioid receptor antagonist) and cetirizine (H1-blocking agent), naltrexone was found to significantly reduce both itching and alloknesis. Cetirizine reduced focal itch but failed to influence the alloknesis phenomenon. The wheal and flare reaction was suppressed only by cetirizine. These different effects point to a mainly CNS-based activity of naltrexone but a peripheral level effect of cetirizine. Due to long-lasting experience with group sport as a supporting adjuvant for inpatients with AE, we evaluated, by clinical, psychometric, and physiological studies, the therapeutic efficacy of controlled physical exercise in addition to otherwise equal anti-eczematous therapy for both voluntary participants and non-participants in sports by performing several case-control studies, one followed-up to 6 months after the patients' discharge from the hospital. Regular moderate exercises neither deteriorated nor impeded the recovery from AE, ameliorated the participants' scratch controlling ability and significantly their depressed emotional mood. The non-participants failed to achieve these aims. Sweating-induced itch was inhibited in almost all participants if simple skin care (clearing by warm shower, ointment) and short-term rest were used by informed patients. In conclusion, there are several indications that itching is elicited in individuals inclined to cutaneous atopy, regardless of their eczematous or just eczema-free state, by a different physiological pathway from that in non-atopic individuals. Therefore, antipruritic agents influencing the centrally altered nociception of atopics are needed and may be expected in near future. (ABSTRACT TRUNCATED)
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PMID:Recent studies of cutaneous nociception in atopic and non-atopic subjects. 1009 77

Cannabis has been used for centuries in the medicinal treatment of gastrointestinal disorders. Endogenous cannabinimimetic substances such as 2-arachidonylglycerol have been isolated from gut homogenates and CB1-cannabinoid binding sites have been identified in small intestine. In this study, CB1-cannabinoid receptors (CB1-R) were immunohistochemically localized within the enteric nervous system of the pig, an omnivorous species whose digestive tract is functionally similar to humans. Two anti-CB1-R antisera, raised against N-terminal epitopes in the human CB1-R, were employed to localize receptor immunoreactivity by secondary immunofluorescence. CB1-R immunoreactivity was observed in the myenteric and submucosal ganglionated plexuses of porcine ileum and colon. In the ileum, all CB1-R-immunoreactive neurons coexpressed immunoreactivity to the cholinergic marker, choline acetyltransferase (ChAT). CB1-R/ChAT-immunoreactive neurons appeared to be in close apposition to ileal Peyer's patches, submucosal blood vessels, and intestinal crypts. In the distal colon, CB1-R-immunoreactive neurons also expressed immunoreactivity to ChAT, albeit less frequently than in ileum. Immunoreactivity to vasoactive intestinal peptide or nitric oxide synthase was not colocalized in ileal or colonic CB1-R-immunoreactive neurons. These studies indicate that CB1-R are present in cholinergic neurons in the porcine enteric nervous system. The potential roles of these receptors in intestinal motility and epithelial transport, host defense and visceral pain transmission are discussed.
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PMID:Localization of CB1-cannabinoid receptor immunoreactivity in the porcine enteric nervous system. 1107 17

The cerebral circulation is innervated by sympathetic, parasympathetic, and sensory nerves, which store a considerable number of neurotransmitters. The role of these has been evaluated in primary headaches. A clear association between head pain and the release of calcitonin gene-related peptide was demonstrated. In cluster headache and in a case of chronic paroxysmal headache there was in addition the release of vasoactive intestinal peptide, which was associated with the facial symptoms (nasal congestion, rhinorrhea). In parallel with sumatriptan treatment, head pain subsided and neuropeptide release normalized. These data show the involvement of sensory and parasympathetic mechanisms in the pathophysiology of primary headaches.
Curr Pain Headache Rep 2001 Feb
PMID:Pathophysiology of primary headaches. 1125 41

Several lines of evidence support involvement of the parasympathetic system in migraine: (i) migraine-associated symptoms, such as exaggerated facial flushing, lacrimation and rhinorrhea; (ii) increased levels of cranial venous vasoactive intestinal peptide in migraineurs during attacks; and (iii) reports of migraine pain alleviation by intranasal instillation of lidocaine, which can block some of the parasympathetic outflow to the cranium. This study assessed cranial parasympathetic function in migraineurs in between attacks, assuming that abnormal function might imply involvement of the parasympathetics in migraine pathogenesis. We tested 39 female migraineurs outside attacks, of whom 11 had bilateral pain, 20 unilateral at a specific side and eight alternating unilateral head pain, and 16 controls. The trigemino-parasympathetic reflex was studied, using soapy and saline eye drops for stimulation of the afferent limb of the reflex arch, and cutaneous vascular response at the forehead for the efferent limb. The latter was recorded by photoplethysmography on both sides of the forehead. We found no difference in vasodilatation between migraineurs as a group and controls (83.7 +/- 6.5% and 80.8 +/- 7.6%, respectively, not significant). However, when analysing data by the site of pain, we found that those with bilateral pain had the largest vasodilatation response (141.6 +/- 16.2%, P < 0.05 versus controls, analysis of varance, post hoc Tukey-Kramer HSD), while those with unilateral pain had the least vasodilatation (45.5 +/- 3.3%, P < 0.05). The response of patients with alternating pain (97.2 +/- 12.6%) did not differ from controls. It is concluded that cranial parasympathetic function does differ among patients with various migraine types at rest. Based on the understanding of dysfunctional brainstem pain modulation in migraine, we suggest a model of within-brainstem interaction between the two locus coeruleus nuclei, which are involved in control of pain and cranial parasympathetic outflow. The model assumes various levels of inhibitory inter-relationships between these two nuclei; diminution or absence of the normal reciprocal inhibitory relationships between them may underlie the augmented cranial parasympathetic response in bilateral migraineurs, while an excess of reciprocal inhibitory relationship between them may underlie the diminished cranial parasympathetic response in unilateral migraineurs. These findings might help in clarifying inter-relationships between brainstem nuclei in the context of migraine pathogenesis.
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PMID:Different patterns of parasympathetic activation in uni- and bilateral migraineurs. 1280 17


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