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

Animal studies have established a role for the brainstem reticular formation, in particular the rostral ventromedial medulla (RVM), in the development and maintenance of central sensitisation and its clinical manifestation, secondary hyperalgesia. Similar evidence in humans is lacking, as neuroimaging studies have mainly focused on cortical changes. To fully characterise the supraspinal contributions to central sensitisation in humans, we used whole-brain functional magnetic resonance imaging at 3T, to record brain responses to punctate mechanical stimulation in an area of secondary hyperalgesia. We used the heat/capsaicin sensitisation model to induce secondary hyperalgesia on the right lower leg in 12 healthy volunteers. A paired t-test was used to compare activation maps obtained during punctate stimulation of the secondary hyperalgesia area and those recorded during control punctate stimulation (same body site, untreated skin, separate session). The following areas showed significantly increased activation (Z>2.3, corrected P<0.01) during hyperalgesia: contralateral brainstem, cerebellum, bilateral thalamus, contralateral primary and secondary somatosensory cortices, bilateral posterior insula, anterior and posterior cingulate cortices, right middle frontal gyrus and right parietal association cortex. Brainstem activation was localised to two distinct areas of the midbrain reticular formation, in regions consistent with the location of nucleus cuneiformis (NCF) and rostral superior colliculi/periaqueductal gray (SC/PAG). The PAG and the NCF are the major sources of input to the RVM, and therefore in an ideal position to modulate its output. These results suggest that structures in the mesencephalic reticular formation, possibly the NCF and PAG, are involved in central sensitisation in humans.
Pain 2005 Apr
PMID:A role for the brainstem in central sensitisation in humans. Evidence from functional magnetic resonance imaging. 2095 99

In healthy subjects, the brain regions most consistently activated in visceral and somatic pain are the key regions in the central pain matrix,including the mid/anterior insula, subregions of the ACC, PFC, thalamus,and in some cases, pontine regions such as the dorsal pons and PAG. Functional neuroimaging studies have demonstrated evidence of altered regional brain activation responses during visceral and somatic stimuli in IBS that have been associated with perceptual differences. Although perceptual studies have shown increased sensitivity to rectosigmoid distension in IBS, most somatic pain studies have demonstrated normal or decreased sensitivity compared with controls; however, a recent study showed increased sensitivity to thermal heat. Altered brain responses in IBS,particularly to visceral stimuli, include activation of regions concerned with attentional processes and response selection, corticolimbic regions concerned with emotional and autonomic responses to stimuli, and subcortical regions receiving cortical projections from the latter and afferent input from the soma and viscera. Altered activations of these regions also may be present in the absence of a noxious visceral stimulus. Changes in rCBF of some of these regions have been associated with treatment response in IBS. With regard to differences in cortical processing of visceral versus somatic stimuli in IBS, there have been only two studies. Greater activations of the dorsal ACC, thalamus, and PFC have been shown with visceral stimuli compared with somatic stimuli in IBS. A plausible hypothesis for the observations from brain imaging studies is that IBS patients demonstrate a compromised activation of pain inhibition circuits including those of the cortico-pontine circuit but increased activation of limbic and paralimbic circuits that may be related to pain facilitation.
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PMID:Brain responses to visceral and somatic stimuli in irritable bowel syndrome: a central nervous system disorder? 1586 35

Behavioral studies have indicated that GABAergic modulation is involved in the opioid-induced antinociception in the ventrolateral orbital cortex (VLO). The aim of the current study was to examine whether the GABAergic neurons in the rat VLO expressed mu-opioid receptor subtype 1 (MOR1). This study employed immunofluorescence histochemical double-staining technique and showed that a considerable amount of GABA- and MOR1-like immunoreactive neurons existed in layers II-VI in the VLO. Of these GABA-like immunoreactive neurons, 92.0% of them showed MOR1-like immunoreactivities. Similarly, 80.2% of MOR1-like immuoreactive neurons also exhibited GABA-like immunoreactivities. These results provide morphological evidence that opioid-induced antinociception in the VLO might be due to an inhibitory effect by opioid via MOR1 on GABAergic neurons, resulting in disinhibition of VLO projection neurons and leading to activation of the VLO-PAG brainstem descending pain control system to depress the nociceptive inputs at the spinal cord level.
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PMID:GABAergic neurons express mu-opioid receptors in the ventrolateral orbital cortex of the rat. 1589 49

Deep brain stimulation (DBS) has been used to treat intractable pain for over 50 years. Variations in targets and surgical technique complicate the interpretation of many studies. To better understand its efficacy, we performed a meta-analysis of DBS for pain relief. MEDLINE (1966 to February 2003) and EMBASE (1980 to January 2003) databases were searched using key words deep brain stimulation, sensory thalamus, periventricular gray and pain. Inclusion criteria were based on patient characteristics and protocol clarity. Six studies (between 1977-1997) fitting the criteria were identified. Stimulation sites included the periventricular/periaqueductal grey matter (PVG/PAG), internal capsule (IC), and sensory thalamus (ST). The long-term pain alleviation rate was highest with DBS of the PVG/PAG (79%), or the PVG/PAG plus sensory thalamus/internal capsule (87%). Stimulation of the sensory thalamus alone was less effective (58% long-term success) (p < 0.05). DBS was more effective for nociceptive than deafferentation pain (63% vs 47% long-term success; p < 0.01). Long-term success was attained in over 80% of patients with intractable low back pain (failed back surgery) following successful trial stimulation. Trial stimulation was successful in approximately 50% of those with post-stroke pain, and 58% of patients permanently implanted achieved ongoing pain relief. Higher rates of success were seen with phantom limb pain and neuropathies. We conclude that DBS is frequently effective when used in well-selected patients. Neuroimaging and neuromodulation technology advances complicate the application of these results to modern practice. Ongoing investigations should shed further light on this complex clinical conundrum.
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PMID:Deep brain stimulation for pain relief: a meta-analysis. 1599 77

The study of CNS pain-modulating pathways has led to important discoveries about the role of central nociceptive structures such as PAG and hypothalamus in the pathophysiology of episodic and chronic primary headaches. Functional neuroimaging studies have revealed that primary headaches are characterised by different patterns of activation of central pain modulatory structures. A future model of headache pathophysiology investigating the contribution of CNS pain-modulating pathways will probably increase our understanding of pain processing in primary headaches. Herein we review the neurophysiological approaches to assess central pain modulation in primary headaches with emphasis on the diffuse noxious inhibitory control, a form of endogenous pain inhibition. In addition, patients' data will be presented that highlights the utility of such methods for primary headache's pathophysiology and clinical monitoring.
J Headache Pain 2005 Sep
PMID:Neurophysiological approach to central pain modulation in primary headaches. 1636 61

We conducted a retrospective analysis of long-term results of deep brain stimulation (DBS) for the treatment of neuropathic pain. Twenty-one patients had electrodes implanted in the ventrocaudalis thalamic nucleus (Vc) (n=13) or in both Vc and periaqueductal/periventricular gray matter (PAG/PVG) (n=8). After insertion of the electrodes, 9 patients (43%) had a substantial reduction in pain scores in the absence of stimulation (insertional effect). The effects of stimulation were studied right after surgery or upon return of the patients' pain after electrode insertion (stimulation trials). Patients with a greater than 50% reduction in pain scores were implanted with a pulse generator (IPG). Of interest, patients who had an insertional effect had a trend towards a successful stimulation trial (p=0.08). Overall, 13 of the 21 patients operated (62%) had a successful stimulation trial and received an IPG (12 with electrodes in Vc and one in both Vc and PAG/PVG). Seven patients (33%) did not benefit from stimulation and had the electrodes removed. One patient experienced a prolonged insertional effect and has not required stimulation. Of the 13 patients that received an IPG, 8 discontinued stimulation during the first year of treatment. Only 5 patients maintained long-term benefit (4 with stimulation in Vc and one in both Vc and PAG/PVG). The relatively low efficacy of DBS for the treatment of neuropathic pain stresses the need for further investigation and the exploration of new surgical targets.
Pain 2006 Nov
PMID:Deep brain stimulation for chronic neuropathic pain: long-term outcome and the incidence of insertional effect. 1679 42

Morphine and other opiates are successful treatments for pain, but their usefulness is limited by the development of tolerance. Given that recent studies have observed differential sensitivity to drugs of abuse in adolescents, the aim of this study was to assess antinociceptive tolerance to morphine in adolescent rats using both behavioral and cellular measures. Early (28-35 days postnatal) and late (50-59 days) adolescent and adult (73-75 days) male rats were injected with morphine (5 mg/kg, s.c.) or saline twice a day for two consecutive days. On Day 3, tolerance to morphine was evident in morphine-pretreated rats when tested on the hot plate test. Although baseline latencies for the early compared to late adolescent rats were faster, the magnitude of the shift in ED(50) for morphine was similar for the two adolescent groups. However, the shift in ED(50) tended to be greater in adolescent compared to adult rats. Subsequent to behavioral testing, whole cell patch-clamp recordings were made from ventrolateral PAG neurons. The opioid agonist, met-enkephalin (ME), activated similar outward currents in PAG neurons of early and late adolescent rats. However, reversal potentials of ME-induced currents were shifted to more hyperpolarized potentials in cells from morphine-pretreated rats. In addition, ME induced larger currents in morphine-pretreated rats with faster hot plate latencies compared to the mean (more tolerant) than in rats with slower latencies. These results indicate that repeated intermittent administration of morphine produces tolerance in adolescent rats that is associated with novel changes in opioid-sensitive ventrolateral PAG neurons.
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PMID:Behavioral and electrophysiological evidence for opioid tolerance in adolescent rats. 1682 89

The mesencephalic dorsolateral periaqueductal gray (dlPAG) mediates different modalities of aversive behaviors including pain and nociception and is anatomically delineated from other columns of the PAG by its content of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d). In many brain regions, neuronal NADPH-d is a nitric oxide (NO) synthase (NOS) and NO production mediates many nociceptive and aversive behavioral responses. The aim of this study was to determine how the noxious stimulant capsaicin affects intracellular dynamics in the dlPAG evidenced by Fos protein immunoreactivity (index of intracellular activation) and the NADPH-d reactivity. The basic hypothesis tested was that the effect of systemic capsaicin administration involved activation of the NO-producing machinery in the dlPAG. Compared to vehicle, capsaicin (50mg/kg, subcutaneous) significantly increased NADPH-d reactivity and Fos expression along the dlPAG neuraxis. However, less than one percent of the capsaicin-induced Fos activation occurred in NADPH-d-positive cells. This suggests that different intracellular mechanisms involving NO and activation of at least one other transmitter substance underlie the effects of capsaicin in the dlPAG. Although NADPH-d is a marker for constitutive NOS, only about two-thirds of the NADPH-d-positive neurons in the dlPAG were colocalized with neuronal NOS immunoreactive cells. This observation suggests that in contrast to other brain regions, neuronal NOS is unlikely to account for all NADPH-d activity in the dlPAG. Taken together, the present results show that the effect of capsaicin requires activation of at least one other transmitter and NADPH-d-dependent NO synthesis involving, but not limited to, the neuronal NOS isoform.
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PMID:Acute capsaicin injection increases nicotinamide adenine dinucleotide phosphate diaphorase staining independent of Fos activation in the rat dorsolateral periaqueductal gray. 1683 9

Previous neuroimaging studies have shown brain activity during not only the application of noxious stimuli, but also prior to stimulation. The functional significance of the anticipatory response, however, has yet to be explored. Two theoretical responses involve either a decrease or an increase in sensitivity of the nociceptive system. In a functional magnetic resonance imaging (fMRI) study, brainstem responses during anticipation and processing of thermal noxious stimuli were investigated. Twelve healthy subjects were warned prior to and then received noxious stimulation to their left hand. Behavioral data showed a positive correlation between the intensity of anticipation and pain. FMRI data revealed brainstem activation in the PAG during the anticipation period. When correlated with individual anticipation ratings, activation during anticipation included significant clusters within the entorhinal cortex and ventral tegmental area (VTA). During receipt, activation within the brainstem included the PAG, VTA, rostral ventromedial medulla (RVM), and the parabrachial nucleus (PB), all elements of descending pain pathways. Using a backward model approach, we explored the functional significance of the anticipatory neural response for subsequent pain processing. Results of this regression analysis revealed that insula activity during receipt was predicted by activity in both the entorhinal cortex and VTA during anticipation. We suggest that activation in both regions before and during pain may underlie anticipation and subsequent pain modulatory responses, possibly involving the appraisal and control of attention necessary for pain modulation. Together, the results suggest a possible role of brainstem areas in anticipatory mechanisms involved in the maintenance of chronic pain.
Pain 2007 Mar
PMID:Anticipatory brainstem activity predicts neural processing of pain in humans. 1707 Sep 96

In this study, the effect of (S)-3,4-dicarboxyphenylglycine (DCPG), a selective mGlu8 receptor agonist, has been investigated in inflammatory and neuropathic pain models in order to elucidate the role of mGlu8 receptor in modulating pain perception. Inflammatory pain was induced by the peripheral injection of formalin or carrageenan in awake mice. Systemic administration of (S)-3,4-DCPG, performed 15 min before formalin, decreased both early and delayed nociceptive responses of the formalin test. When this treatment was carried out 15 min after the peripheral injection of formalin it still reduced the late hyperalgesic phase. Similarly, systemic (S)-3,4-DCPG reduced carrageenan-induced thermal hyperalgesia and mechanical allodynia when administered 15 min before carrageenan, but no effect on pain behaviour was observed when (S)-3,4-DCPG was given after the development of carrageenan-induced inflammatory pain. When microinjected into the lateral PAG (RS)-alpha-methylserine-O-phoshate (MSOP), a group III receptor antagonist, antagonised the analgesic effect induced by systemic administration of (S)-3,4-DCPG in both of the inflammatory pain models. Intra-lateral PAG (S)-3,4-DCPG reduced pain behaviour when administered 10 min before formalin or carrageenan; both the effects were blocked by intra-lateral PAG MSOP. (S)-3,4-DCPG was ineffective in alleviating thermal hyperalgesia and mechanical allodynia 7 days after the chronic constriction injury of the sciatic nerve, whereas it proved effective 3 days after surgery. Taken together these results suggest that stimulation of mGlu8 receptors relieve formalin and carrageenan-induced hyperalgesia in inflammatory pain, whereas it would seem less effective in established inflammatory or neuropathic pain.
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PMID:Effects of (S)-3,4-DCPG, an mGlu8 receptor agonist, on inflammatory and neuropathic pain in mice. 1711 12


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