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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The analgesic actions of opioids are in large part mediated by activation of brainstem pain modulating neurons that depress nociceptive transmission at the level of the dorsal horn. The present study was designed to characterize the contribution of N-methyl-D-aspartate (NMDA)- and non-NMDA-mediated excitatory transmission within the rostral ventromedial medulla (RVM) to the activation of brainstem inhibitory output neurons and analgesia produced by systemic morphine administration. The NMDA receptor antagonist D-2-amino-5-phosophonopentanoic acid (AP5), the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione disodium (CNQX) or saline was infused into the RVM of lightly anesthetized rats while recording the activity of identified pain modulating neurons: 'off-cells', thought to inhibit nociceptive transmission, and 'on-cells', thought to facilitate nociception. Nociceptive responsiveness (tail flick latency) was not affected by either antagonist. AP5, but not CNQX, attenuated or blocked activation and disinhibition of off-cells and the antinociception produced by systemically administered morphine. Reflex-related discharge of on-cells was unaffected by AP5, but significantly attenuated by CNQX. The present results highlight two important aspects of RVM pain modulatory circuits. First, morphine given systemically produces its analgesic effect at least in part by recruiting an NMDA-mediated excitatory process to activate off-cells within the RVM. This excitatory process may play a role in the analgesic synergy produced by simultaneous mu-opioid activation at different levels of the neuraxis. Second, reflex-related activation of on-cells is mediated by a non-NMDA receptor, and this activation does not appear to play a significant role in regulating reflex responses to acute noxious stimuli. Excitatory amino acid-mediated excitation thus has at least two distinct roles within the RVM, activating off-cells and on-cells under different conditions.
Pain 2001 May
PMID:Activation of brainstem N-methyl-D-aspartate receptors is required for the analgesic actions of morphine given systemically. 1132 34

We have examined a hemispherectomized patient who complained of touch-evoked pricking and burning pain in her paretic hand, especially when the hand was cold. Psychophysical examination showed that for the paretic side she confused cool and warm temperatures, and confirmed that she had a robust allodynia to brush stroking that was enhanced at a cold ambient temperature. Functional magnetic resonance imaging (fMRI) showed that during brush-evoked allodynia, brain structures implicated in normal pain processing (viz. posterior part of the anterior cingulate cortex, secondary somatosensory cortex, and prefrontal cortices) were activated. The fMRI findings thus indicate that the central pain in this patient was served by brain structures implicated in normal pain processing. Possible pathophysiological mechanisms include plasticity as well as thalamic disinhibition.
Eur J Pain 2001
PMID:Central pain in a hemispherectomized patient. 1146 86

Previous studies found that stressful events during pregnancy can alter the offspring's pain sensitivity to the phasic nociceptive stimuli. The present data constitute the first demonstration of the consequences of prenatal stress to formalin-induced pain in juvenile rats. Injection of formalin into a hind paw of a 25-day-old rat that had not been stressed prenatally produced the typical biphasic specific nociceptive behavioral response consisting of an early short phase lasting 1-4 min followed by a second prolonged phase (12-24 min). Between them there was an interphase that lasted 6-9 min during which the specific behaviors were not shown. This period is generally considered to be a period of inactivity. Prenatally stressed rat pups showed significant increase in flexing+shaking behaviors and in the duration of the second phase of formalin-induced pain in flexing+shaking and licking behaviors and decrease of the duration of the interphase. Disinhibition of the pain behaviors during the interphase was greatly more pronounced in female than in male rats. Sex differences indicate increased vulnerability of inhibitory processes to prenatal stress in females compared with males. These data also underline the importance of understanding the nature of the interphase and provide data on the mechanisms that underlie that component of the formalin test.
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PMID:Prenatal stress alters time characteristics and intensity of formalin-induced pain responses in juvenile rats. 1157 23

The periaqueductal grey (PAG) region of the brainstem is a known modulator of somatic pain transmission. Migraine is likely to be due to episodic brain dysfunction in pathways involved in the control of pain and other sensory modalities, such as light and sound. To investigate the influence of the PAG on pain transmission from intracranial structures, we examined spinal trigeminal neuronal activity in response to PAG stimulation in a model of trigeminovascular nociception in the cat. Evoked trigeminal neuronal activity in the spinal cord was reversibly inhibited by stimulation of the PAG. The effect was robust with a mean reduction in evoked activity of -61+/-21%. This effect could be seen both ipsilateral and contralateral to the side of PAG stimulation and was well localised to the ventrolateral PAG. These data demonstrate that a role of the PAG is to inhibit afferent trigeminal nociceptive traffic. Considered with neurosurgical and human functional imaging studies, these data support the notion that brainstem dysfunction might lead to disinhibition of trigeminal afferents and be important in the pain process of migraines.
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PMID:The periaqueductal grey matter modulates trigeminovascular input: a role in migraine? 1168 64

Traditionally, neuropathic pain has been classified due to aetiology of nerve damage-traumatic, inflammatory or metabolic, for instance. Based on this classification, pain therapy often is insufficient. Recent research revealed different mechanisms, which are responsible for the generation of pain after nerve lesion. These mechanisms seem to be independent of aetiology of the nerve damage. The most important mechanisms are accumulation of sodium channels on injured nerves, pathological sympatho-afferent coupling, disinhibition of nociception and central or peripheral nociceptive sensitisation. Each individual mechanism could be treated specifically by current available drugs, or by non-drug therapy. However, future research has to focus on exploring tools to recognise individual pain mechanisms in single patients. Thereby treatment will become more effective.
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PMID:[Mechanism-based treatment principles of neuropathic pain]. 1182 25

A specialized subpopulation of unmyelinated chemonociceptors and dedicated spinal neurons which are responsible for the itch sensation have been identified recently. Under physiological conditions, painful stimuli such as activation of conventional mechano-heat-sensitive ('polymodal') nociceptors (scratching) inhibit the itch sensation via central mechanisms. Conversely, centrally acting pain-inhibiting opioids enhance itch by disinhibition. These mechanisms might well explain the itch in diseases characterized by histamine release like urticaria, and might provide evidence for the role of endogenous opioids as central itch promotors in cholestasis or nephropathy. After the discovery of itch-specific neurons has dramatically improved our understanding of itch mechanisms under experimental conditions, the present task is to correlate these new findings to the clinical situation of itch patients.
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PMID:Itch--mediators and mechanisms. 1185 46

The pharmacological effects of the opioid analgesics are derived from their complex interactions with three opioid receptor types (mu, delta, and kappa; morphine is an agonist at the mu opioid receptor). These receptors are found in the periphery, at presynaptic and postsynaptic sites in the spinal cord dorsal horn, and in the brain stem, thalamus, and cortex, in what constitutes the ascending pain transmission system, as well as structures that comprise a descending inhibitory system that modulates pain at the level of the spinal cord. The cellular effects of opioids include a decrease in presynaptic transmitter release, hyperpolarization of postsynaptic elements, and disinhibition. The endogenous opioid peptides are part of an endogenous pain modulatory system. A number of opioids are available for clinical use, including morphine, hydromorphone, levorphanol, oxymorphone, methadone, meperidine, oxycodone, and fentanyl, and their advantages and disadvantages for the management of pain are discussed. An understanding of the pharmacokinetic properties, as well as issues related to opioid rotation, tolerance, dependence, and addiction are essential aspects of the clinical pharmacology of opioids for pain.
Clin J Pain
PMID:Clinical pharmacology of opioids for pain. 1247 50

According to the classification criteria proposed by the American College of Rheumatology, fibromyalgia is a long-standing multifocal pain condition combined with generalised allodynia/hyperalgesia. It is the generalised allodynia/hyperalgesia that distinguishes fibromyalgia from other conditions with chronic musculoskeletal pain. Central sensitisation of nociceptive neurons in the dorsal horn due to activation of N-methyl-D-aspartic acid receptors and disinhibition of pain due to deficient function of the descending inhibitory system are probable pathogenic factors for allodynia/hyperalgesia. Furthermore, chronic pain is a chronic emotional and physical stressor. Chronic stress and chronic sleep disturbance are not specific for fibromyalgia but could be the causes of symptoms like fatigue, cognitive difficulties and other stress-related symptoms. They may also cause neuroendocrinological and immunological aberrations.
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PMID:Fibromyalgia--from syndrome to disease. Overview of pathogenetic mechanisms. 1281 64

Modern pain-control theory predicts that a loss of inhibition (disinhibition) in the dorsal horn of the spinal cord is a crucial substrate for chronic pain syndromes. However, the nature of the mechanisms that underlie such disinhibition has remained controversial. Here we present evidence for a novel mechanism of disinhibition following peripheral nerve injury. It involves a trans-synaptic reduction in the expression of the potassium-chloride exporter KCC2, and the consequent disruption of anion homeostasis in neurons of lamina I of the superficial dorsal horn, one of the main spinal nociceptive output pathways. In our experiments, the resulting shift in the transmembrane anion gradient caused normally inhibitory anionic synaptic currents to be excitatory, substantially driving up the net excitability of lamina I neurons. Local blockade or knock-down of the spinal KCC2 exporter in intact rats markedly reduced the nociceptive threshold, confirming that the reported disruption of anion homeostasis in lamina I neurons was sufficient to cause neuropathic pain.
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PMID:Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain. 1293 Nov 88

This study examined patterns of emotional and behavioural sequelae in 300 individuals who sustained a traumatic brain injury (TBI). Participants were obtained through the Adult Acquired Brain Injury Program at Chedoke Hospital in Hamilton, Ontario, based on the following inclusionary criteria: (1) single incident of TBI; (2) no history of additional neurological diseases; (3) time postinjury < or =8.5 years; (4) WAIS-R FSIQ >85 and/or estimated reading skills above grade 5 level; and (5) valid Minnesota Multiphasic Personality Inventory (MMPI) profiles (i.e., F<90, L<66, and K<66). MMPI profiles of these individuals, in randomly split samples of 150 per group, were subjected to a three-step cluster analytic approach. A six-cluster solution was adequately replicated across samples and across clustering techniques. The identified subtypes included profiles indicative of: (1) no concerns or normal functioning; (2) mild somatic and pain concerns; (3) mild internalizing difficulties; (4) marked disinhibition and externalizing behavioural difficulties; (5) marked internalizing difficulties; and (6) marked somatic, internalizing, and externalizing behavioural disturbances. Members of the Externalized subtype were significantly younger in age than those in the other five subtypes, and more likely to be single than those in the Internalized subtype. Individuals in the Internalized subtype tended to be married, have longer times postaccident, and lower WAIS-R Verbal Intelligence Quotients than those comprising the Normal subtype.
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PMID:Subtypes of emotional and behavioural sequelae in patients with traumatic brain injury. 1368 Apr 39


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