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)

Although migraine is characterised by an abnormal cortical excitability level, whether the central nervous system is hyper- or hypo-excitable in migraine still remains an unsolved problem. The aim of our study was to compare the somatosensory evoked potential (SEP) recovery cycle, a marker of the somatosensory system's excitability, in a group of 15 children suffering from migraine without aura (MO) (mean age 11.7+/-1.6 years, five males, 10 females) and 10 control age-matched subjects (CS) (mean age 10.9+/-2.1 years, six males, four females). We calculated the SEP's latency and amplitude modifications after paired electrical stimuli at 5, 20 and 40 ms interstimulus intervals (ISIs), comparing it with a single stimulus condition assumed as the baseline. In MO patients, the amplitudes of the cervical N13 and of the cortical N20, P24 and N30 responses at 20 and 40 ms ISIs showed a higher recovery than in CS (two-way ANOVA, P<0.05). Since, the SEP recovery cycle depends on the inhibitory interneuron function, our findings suggest that a somatosensory system disinhibition takes place in migraine. This is a generalized phenomenon, not limited to the cerebral cortex, but concerning also the cervical grey matter. The SEP recovery cycle reflects the intracellular concentration of Na(+), therefore, the shortened recovery cycle in our MO patients suggests a high level of intracellular Na(+) and a consequent depolarized resting membrane potential, possibly due to an impaired Na(+) -K(+) ATPase function in migraine.
Pain 2005 Nov
PMID:Multilevel somatosensory system disinhibition in children with migraine. 1620 23

In the ventrolateral periaqueductal gray (PAG), activation of excitatory output neurons projecting monosynaptically to OFF cells in the rostral ventromedial medulla (RVM) causes antinociceptive responses and is under the control of cannabinoid receptor type-1 (CB1) and vanilloid transient receptor potential vanilloid type 1 (TRPV1) receptors. We studied in healthy rats the effect of elevation of PAG endocannabinoid [anandamide and 2-arachidonoylglycerol (2-AG)] levels produced by intra-PAG injections of the inhibitor of fatty acid amide hydrolase URB597 [cyclohexylcarbamic acid-3'-carbamoyl-biphenyl-3-yl ester] on 1) nociception in the "plantar test" and 2) spontaneous and tail-flick-related activities of RVM neurons. Depending on the dose or time elapsed since administration, URB597 (0.5-2.5 nmol/rat) either suppressed or increased thermal nociception via TRPV1 or CB1 receptors, respectively. TRPV1 or cannabinoid receptor agonists capsaicin (6 nmol) and (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3,-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate [WIN55,212-2 (4 nmol)] also suppressed or enhanced nociception, respectively. URB597 dose dependently enhanced PAG anandamide and 2-AG levels, with probable subsequent activation of TRPV1/CB1 receptors and only CB1 receptors, respectively. The TRPV1-mediated antinociception and CB1-mediated nociception caused by URB597 correlated with enhanced or reduced activity of RVM OFF cells, suggesting that these effects occur via stimulation or inhibition of excitatory PAG output neurons, respectively. Accordingly, several ventrolateral PAG neurons were found by immunohistochemistry to coexpress TRPV1 and CB1 receptors. Finally, at the highest doses tested, URB597 (4 nmol/rat) and, as previously reported, WIN55,212-2 (25-100 nmol) also caused CB(1)-mediated analgesia, correlating with stimulation (possibly disinhibition) of RVM OFF cells. Thus, endocannabinoids affect the descending pathways of pain control by acting at either CB1 or TRPV1 receptors in healthy rats.
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PMID:Elevation of endocannabinoid levels in the ventrolateral periaqueductal grey through inhibition of fatty acid amide hydrolase affects descending nociceptive pathways via both cannabinoid receptor type 1 and transient receptor potential vanilloid type-1 receptors. 1628 79

Itch is one of the alarm sensations that human beings have phylogenetically evolved for a defense purpose. Many theories and evidences regarding the biological, pathophysiological, and clinical aspects have been given, but an update on the neuroanatomy paths and consequent treatments is required. Some chemicals that are released after skin injury and facilitate the inflammatory process can induce itch or pain or basically lead to a sensitization of the nociceptor response. In clinical practice, the present authors note a continuum of sensations from touch to pain, among which many metaesthetic sensations can be described, even if the patients themselves cannot precisely define them. The specificity of itch neurons is therefore based on their spinal connections to the itch pathway rather than on unique peripheral receptors. The ambiguity of "itch unit" discharge to pruritics and algogens may be solved by the central inhibition of itch by pain: it is common knowledge that scratching relieves itching. Conversely, centrally acting pain-inhibiting opioids enhance itch by disinhibition. The relation between itch and pain is interesting in its clinical and physiopathological aspects in order to select appropriate treatment.
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PMID:Itch, pain, and metaesthetic sensation. 1629 2

The aim of the study was to investigate if contrast enhanced ultrasound (US) imaging of muscular blood flow during and following exercise could detect alterations in vascularity in fibromyalgia (FM) patients. Ten FM patients and 10 matched controls were examined with US during standardised static and directly following static and dynamic muscular contractions of the infraspinatus muscle. Doppler ultrasound evaluation was performed before and after the administration of ultrasound contrast media. The FM patients had lower magnitude of muscle vascularity following dynamic (p<0.001) and during (p<0.002) static exercise compared to controls. The immediate flow response to muscular activity was not only of a lower magnitude, but also of a shorter duration in FM patients following dynamic exercise (p<0.001) and during static exercise (p<0.01). There were no statistically significant group differences in blood flow intensity or duration following static contraction. In conclusion, contrast enhanced US was found useful to study real-time muscle blood flow changes during and following standardised, low-intensity exercise in FM patients and healthy controls. Our results support the suggestion that muscle ischemia can contribute to pain in FM, possibly by maintaining the central nervous changes such as central sensitisation/disinhibition. US with contrast can be a new valuable approach to assess muscle perfusion in pain patients during standardised exercise.
Eur J Pain 2006 Feb
PMID:Decreased muscle blood flow in fibromyalgia patients during standardised muscle exercise: a contrast media enhanced colour Doppler study. 1631 Jul 17

Although glycine receptor Cl- channels (GlyRs) have long been known to mediate inhibitory neurotransmission onto spinal nociceptive neurons, their therapeutic potential for peripheral analgesia has received little attention. However, it has been shown that alpha3-subunit-containing GlyRs are concentrated into regions of the spinal cord dorsal horn where nociceptive afferents terminate. Furthermore, inflammatory mediators specifically inhibit alpha3-containing GlyRs, and deletion of the murine alpha3 gene confers insensitivity to chronic inflammatory pain. This strongly implicates GlyRs in the inflammation-mediated disinhibition of centrally projecting nociceptive neurons. Future therapies aimed at specifically increasing current flux through alpha3-containing GlyRs may prove effective in providing analgesia.
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PMID:Glycine receptors: a new therapeutic target in pain pathways. 1642 71

The pathophysiology of central pain syndromes is still poorly understood and their treatment remains a major challenge. It has long been suggested that lesions of the spinothalamic pathways are necessary for developing these pain syndromes. The recently proposed thermosensory disinhibition theory suggests that reduction of the inhibition of thermal sensory afferents that affect nociceptive systems may play a major pathophysiological role. Syringomyelia, which is frequently associated with central neuropathic pain, is characterized by a selective or preferential lesion of the spinothalamic tract resulting in thermosensory deficits of various extents and magnitudes. Thus, syringomyelia represents a unique 'pathological model' particularly suited to investigating the relationship between spinothalamic tract dysfunction, thermosensory deficits and pain. Here, we systematically compared the sensory loss (thermal and mechanical), using quantitative sensory testing, between 46 consecutive syringomyelia patients with or without neuropathic pain. We then further investigated the mechanisms of evoked pains in these patients, using functional MRI (fMRI) in a subgroup of patients with cold or brush-evoked allodynia, compared with patients without pain and healthy volunteers. We found no significant difference in the magnitude or extent of sensory deficits between patients with or without neuropathic pain, suggesting that lesions of the spinothalamic pathways are not sufficient for developing central pain. However, a different pattern of sensory deficits was observed between patients with spontaneous pain only (n = 11) and patients with both spontaneous pain and allodynia (n = 20), suggesting that the mechanisms of central pain are not univocal. In patients with spontaneous pain only, the thermal sensory loss was significantly more asymmetrical and there was a direct relationship between the extent of thermosensory deficits (i.e. deafferentation) and the intensity of burning pain. In contrast, patients with allodynia had reduced thermal deficits, in terms of both magnitude and extent. In addition, the sensory deficits were different between patients with cold or tactile allodynia, suggesting distinct pathophysiological mechanisms related to the sub-modalities of allodynia. Our fMRI study further confirmed this, showing that different sub-types of allodynia were associated with distinct patterns of brain activity, which do not necessarily correspond to the 'pain matrix' involved in acute physiological pain. The prefrontal cortex was the only area consistently activated by pathological evoked pains, suggesting that alteration of high-level pain modulatory mechanisms might play a major role in allodynia due to central lesion.
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PMID:Mechanisms of central neuropathic pain: a combined psychophysical and fMRI study in syringomyelia. 1643 17

This article reviews the literature on the relationship between interpersonal rejection and aggression. Four bodies of research are summarized: laboratory experiments that manipulate rejection, rejection among adults in everyday life, rejection in childhood, and individual differences that may moderate the relationship. The theoretical mechanisms behind the effect are then explored. Possible explanations for why rejection leads to anger and aggression include: rejection as a source of pain, rejection as a source of frustration, rejection as a threat to self-esteem, mood improvement following aggression, aggression as social influence, aggression as a means of reestablishing control, retribution, disinhibition, and loss of self-control.
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PMID:Interpersonal rejection as a determinant of anger and aggression. 1676 50

Chronic fibromyalgia (FM) pain is prevalent (estimated as high as 13%), predominantly affects women, and is associated with a variety of focal pain conditions. Ongoing FM pain is referred to deep tissues and is described as widespread but usually is maximally located within a restricted region such as the shoulders. Palpation of deep tissues reveals an enhanced nociceptive sensitivity that is not restricted to regions of clinical pain. Similarly, psychophysical testing reveals allodynia and hyperalgesia for cutaneous stimulation at locations beyond regions of clinical pain referral. The combination of widely distributed clinical pain and generalized hypersensitivity is highly disabling, but no satisfactory treatment is regularly prescribed. A thorough understanding of mechanisms will likely be required to develop and document adequate therapies. The generalized hypersensitivity associated with FM has focused considerable interest on central (CNS) mechanisms for the disorder. These include central sensitization, central disinhibition and a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis. However, the central effects associated with FM can be produced by a peripheral source of pain. Chronic nociceptive input induces central sensitization, magnifying pain, and it activates the HPA and the sympathetic nervous system. Chronic sympathetic activation indirectly sensitizes peripheral nociceptors and sets up a vicious cycle. Thus, it appears that central mechanisms of FM pain are dependent on abnormal peripheral input(s) for development and maintenance of this condition. A substantial literature defines peripheral-CNS-peripheral interactions that are integral to FM pain. These reciprocal actions and related phenomena of relevance to FM pain are reviewed here, leading to suggestions for testing of therapeutic approaches.
Pain 2006 Oct
PMID:Mechanisms underlying development of spatially distributed chronic pain (fibromyalgia). 1729 49

Patients with advanced cancer often experience with physical impairment and loss of autonomy sometimes preceding inexorable death. It is that can emerge Suicidal ideation occasionally associated with suicidal attempt can arise in this particular context but also following the initial diagnostic talk and during all the stages of the disease. The risk is often considered twice higher in this patients'group compared to the general population and increases with advanced stages of the disease. Among patients with cancer, suicidal crisis can be expressed as part of a request for euthanasia, physician-assisted suicide and para suicide behaviors. Clues can help the clinician to identify early these vulnerable patients. Therefore, suicidal situations can emerge in the particular context of physical impairment, poor quality of life and poor control of physical symptoms (such as pain, tumoral localization in particular lung, head and neck, pancreas). The association of hopelessness and helplessness and a loss of control of the situation are strongly correlated with the expression of suicidal ideations. The presence of a confusional or psychomotor disinhibition with hallucinations, irrational thoughts and the absence of a libidinal object of investment have also to be taken into account. This suicidal crisis can be considered as a way for the patient to escape an intolerable situation (uncontrolled pain or other symptoms) and maintain self-control and decisional autonomy. Management of suicidal crisis in patients with cancer includes careful attention and legitimization of the patient's distress without inducing any guilt. Appropriate control of physical symptoms is warranted including screening and treating any mood disorder or any organic mental disorder. Treating associated anxiety and making sure that the patient's safety is under control are essential. Last but not the least, involving the whole treatment team is key in preventing transformation of the suicidal crisis into institutional crisis.
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PMID:[Suicidal crisis in oncology: assessment and care]. 1687 80

We review previously published data, and present some new data, indicating that spinal application of neuropeptide Y (NPY) reduces behavioral and neurophysiological signs of acute and chronic pain. In models of acute pain, early behavioral studies showed that spinal (intrathecal) administration of NPY and Y2 receptor agonists decrease thermal nociception. Subsequent neurophysiological studies indicated that Y2-mediated inhibition of excitatory neurotransmitter release from primary afferent terminals in the substantia gelatinosa may contribute to the antinociceptive actions of NPY. As with acute pain, NPY reduced behavioral signs of inflammatory pain such as mechanical allodynia and thermal hyperalgesia; however, receptor antagonist studies indicate an important contribution of spinal Y1 rather than Y2 receptors. Interestingly, Y1 agonists suppress inhibitory synaptic events in dorsal horn neurons (indeed, well known mu-opioid analgesic drugs produce similar cellular actions). To resolve the behavioral and neurophysiological data, we propose that NPY/Y1 inhibits the spinal release of inhibitory neurotransmitters (GABA and glycine) onto inhibitory neurons, e.g. disinhibition of pain inhibition, resulting in hyporeflexia. The above mechanisms of Y1- and Y2-mediated analgesia may also operate in the setting of peripheral nerve injury, and new data indicate that NPY dose-dependently inhibits behavioral signs of neuropathic pain. Indeed, neurophysiological studies indicate that Y2-mediated inhibition of Ca(2+) channel currents in dorsal root ganglion neurons is actually increased after axotomy. We conclude that spinal delivery of Y1 agonists may be of use in the treatment of chronic inflammatory pain, and that the use of Y1 and Y2 agonists in neuropathic pain warrants further consideration.
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PMID:Spinal mechanisms of NPY analgesia. 1719 6


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