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

Background. The brain-gut interaction is important for the understanding of pain mechanisms related to gastroenterological diseases. Unfortunately little is known about the early cerebral events related to the processing of gut-evoked pain. The aims of this human study were (1) to investigate the early-evoked brain potentials (EPs) to painful sigmoid colon stimulation and (2) to evaluate the EPs evoked from the convergent referred skin pain area after this area was induced by the painful gut stimulation. The background for the second aim was to evaluate whether the convergent input between somatic and visceral structures could induce detectable short-term cortical reorganization. Methods. Eleven subjects (nine men) participated; the mean age was 39.5+/-11.9 years. The gut-evoked EPs (recorded from 31 scalp sites) were evoked by electrical stimulation 30 cm from the anal verge by a modified biopsy forceps, inserted through a sigmoidoscope. The painful gut stimulation elicited a characteristic pain pattern referred to the abdomen. The short latency somatosensory evoked potentials were evoked from the skin inside and outside the referred pain area elicited by gut stimulation. A total of 750 electrical stimuli were delivered to the gut at slight painful stimulus intensity and 500 stimuli were delivered to the skin. Results. Short-latency EPs to electrical gut stimulation with an onset of 50-60 ms could be recorded. The gut EP topography revealed three consecutive positive peaks (P63, P101, P145) towards the frontal area. Centroparietal negativities (N128 and N222) were found, which were followed by two central positivities (P269 and P352). The somatic and gut evoked EPs differed in morphology and topography, but the EPs to skin stimulation inside and outside the gut-evoked referred pain area did not differ significantly. Conclusion. Short latency (50-60 ms) EPs to painful electrical sigmoid colon stimulation were demonstrated, reflecting an early cortical processing of sensory input from the sigmoid colon. The early cortical processing of somatic input from experimentally evoked visceral referred pain areas did not cause any detectable short-term cortical reorganization.
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PMID:Short latency cerebral response evoked by painful electrical stimulation applied to the human sigmoid colon and to the convergent referred somatic pain area. 1271 8

Recent clinical studies showed that acute migraine attacks are accompanied by increased periorbital and bodily skin sensitivity to touch, heat and cold. Parallel pre-clinical studies showed that the underlying mechanism is sensitization of primary nociceptors and central trigeminovascular neurons. The present study investigates the sensory state of neuronal pathways that mediate skin pain sensation in migraine patients in between attacks. The assessments of sensory perception included (a) mechanical and thermal pain thresholds of the periorbital area, electrical pain threshold of forearm skin, (b) pain scores to phasic supra-threshold stimuli in the same modalities and areas as above, and (c) temporal summation of pain induced by applying noxious tonic heat pain and brief trains of noxious mechanical and electrical pulses to the above skin areas. Thirty-four pain-free migraine patients and 28 age- and gender-matched controls were studied. Patients did not differ from controls in their pain thresholds for heat (44+/-2.6 vs. 44.6+/-1.9 degrees C), and electrical (4.8+/-1.6 vs. 4.3+/-1.6 mA) stimulation, and in their pain scores for supra-threshold phasic stimuli for all modalities. They did, however, differ in their pain threshold for mechanical stimulation, just by one von Frey filament (P=0.01) and in their pain scores of the temporal summation tests. Increased summation of pain was found in migraineurs for repeated mechanical stimuli (delta visual analog scale (VAS) +2.32+/-0.73 in patients vs. +0.16+/-0.83 in controls, P=0.05) and repeated electrical stimuli (delta VAS +3.83+/-1.91 vs -3.79+/-2.31, P=0.01). Increased summation corresponded with more severe clinical parameters of migraine and tended to depend on interval since last migraine attack. The absence of clinically or overt laboratory expressed allodynia suggests that pain pathways are not sensitized in the pain-free migraine patients. Nevertheless, the increased temporal summation, and the slight decrease in mechanical pain thresholds, suggest that central nociceptive neurons do express activation-dependent plasticity. These findings may point to an important pathophysiological change in membrane properties of nociceptive neurons of migraine patients; a change that may hold a key to more effective prophylactic treatment.
Pain 2003 Aug
PMID:Repeated noxious stimulation of the skin enhances cutaneous pain perception of migraine patients in-between attacks: clinical evidence for continuous sub-threshold increase in membrane excitability of central trigeminovascular neurons. 1292 42

The authors present a case of a 54-year-old woman with a 3-year history of chronic pain syndrome, probably of postherapeutic origin, with diffuse segmentary dermatome characteristics, both somatic and autonomic. The former were exemplified by a constant "burning" skin pain in the representation of Th8-LI dermatomes unilaterally, while the latter by a unilateral visceral pain within the abdominal cavity. Electrophysiological examination indicated a neuropathic origin of the pain, despite the lack of clinically evident sensory deficits and/or hypersensitivity. The pain was so intense that normal walking was difficult for the patient and ineffectiveness of her treatment made her suicidal. Since both pharmacological treatment (non-steroid analgesics, opioids, antidepressants, and anticonvulsants including gabapentin) and minimally invasive methods of treatment (blockades, thermolesions) failed to control pain, she was subjected to surgery. A right-sided DREZ lesion within the Th8-LI dermatomes resulted in a complete pain relief, both within the somatic and autonomic innervation projections, and in the patient's functional recovery.
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PMID:[The DREZ lesion as an effective treatment for chronic hypothetically post-herpetic neuropathic pain. Case report and review of literature]. 1474 52

Butamben (BAB) is a local anesthetic that can be used in epidural suspensions for long-term selective suppression of dorsal root pain signal transmission and in ointments for the treatment of skin pain. Previously, high-voltage activated N-type calcium channel inhibition has been implicated in the analgesic effect of BAB. In the present study we show that low-voltage activated or T-type calcium channels may also contribute to this effect. Typical transient T-type barium currents, selectively evoked by low-voltage (-40 mV) clamp stimulation of small (approximately 20 microm diameter) dorsal root ganglion neurons from newborn mice, were inhibited by BAB with an IC50 value of approximately 200 microM. Furthermore, 200 microM BAB accelerated T-type current activation, deactivation, and inactivation kinetics, comparable to earlier observations for N-type calcium channels. Finally, 200 microM BAB had no effect on the midpoint potential and slope factor of the activation curve, although it caused a approximately 3 mV hyperpolarizing shift of the inactivation curve, without affecting the slope factor. We conclude that BAB inhibits T-type calcium channels with a mechanism associated with channel kinetics acceleration.
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PMID:The local anesthetic butamben inhibits and accelerates low-voltage activated T-type currents in small sensory neurons. 1636 19

Seeking information on the physiological properties of the trigeminal motoneuronal pool we investigated changes in the excitability of trigeminal motor system induced by two types of experimental pain (muscle and skin). In one session, we studied the effect of muscle pain induced by hypertonic saline infusion into the masseter muscle on the recovery cycle of the heteronymous H-reflex in the temporalis muscle and the homonymous silent period (SP) in the masseter muscle, both elicited by stimulation of the masseteric nerve in ten-healthy subjects. In another session, we studied the effect of laser stimuli applied to the perioral region, at conditioning intervals from 20 to 160 ms, on the temporalis H-reflex and masseter SP in nine healthy subjects. Whereas laser-induced skin pain significantly inhibited the temporalis H-reflex and facilitated the masseter SP (P < 0.01), muscle pain left the time course of the temporalis H-reflex and masseter SP unchanged (P > 0.05). The timing of temporalis H-reflex suppression and masseter-SP enhancement induced by laser stimuli indicates that facial skin nociceptors inhibit trigeminal motoneurones via multysynaptic reflex pathways. Hypertonic saline, a stimulus that predominantly activates group III and IV afferents, left both variables reflecting trigeminal motoneuron excitability unchanged. Due to the differences between the two experimental models, we cannot conclude that such inhibitory reflex pathway does not exist from muscle nociceptors to trigeminal motoneurones.
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PMID:Experimental skin pain and muscle pain induce distinct changes in human trigeminal motoneuronal excitability. 1673 7

Various muscle pains constitute a large clinical problem, both for patients and clinicians. Gabapentin is an established therapy in neuropathic pain and reduces cutaneous pain in healthy volunteers. Gabapentin in combination with other analgesics reduces post-operative pain. No data exist on the effect of gabapentin on muscle pain. This study investigates the effect of gabapentin on muscle and cutaneous pain in healthy volunteers. Sixteen healthy volunteers, 8 male/8 female, were included in this double-blind three-session crossover study comparing the effects of 0, 1200, 1800 and 2600 mg (pre-treatment, titrated over 4 doses) gabapentin and placebo. Muscle pain was induced by infusing 0.5 ml of hypertonic saline into the anterior tibial muscle. Simultaneously, subjects graded pain on a computerized visual analog scale (VAS, 0-10). Total (AUC, VAS*duration in s) and maximal pain (VAS(max)) were assessed. Areas of local and referred pain were measured. Further, continuous intracutaneous electrical stimulation was applied to the forearm. Current was increased until pain intensity 5/10 or until subjects reached a cut-off of 70 mA. Spontaneous pain (VAS 0-10), areas of secondary hyperalgesia to pinprick (cm2) and mechanical pain threshold (g) within this area were assessed. Gabapentin pre-treatment reduced sensitivity to electrical induction of skin pain by 14%, p=0.016. Secondary hyperalgesia was induced, but areas were reduced after pre-treatment, p<0.05. Mechanical pain thresholds were unaffected. Pain induced by intramuscular infusion of hypertonic saline was not affected by gabapentin. In conclusion, single or repeated dosing of gabapentin reduced cutaneous but not muscle pain in healthy volunteers.
Pain 2006 Nov
PMID:Multiple dose gabapentin attenuates cutaneous pain and central sensitisation but not muscle pain in healthy volunteers. 1678 Oct 73

The majority of patients in pain clinics are treated for muscle pain yet methods to study it in animals are relatively weak compared to methods to study skin pain. Here we describe an in vitro muscle-nerve preparation and model of muscle ischemia and contractile fatigue in mice. Timed muscle contraction is electrically evoked, while single unit activity of muscle sensory neurons and muscle contractile force are simultaneously recorded. The muscle is placed in a small (<1 mL) chamber where oxygen levels can be manipulated, drugs can be applied, and the extracellular milieu can be highly controlled. We demonstrate that we can record from sensory afferents that have the properties expected of ischemic nociceptors. This method serves for studying the neuronal and molecular mechanisms underlying ischemic pains such as angina, intermittent claudication, and sickle cell crisis.
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PMID:A novel mouse skeletal muscle-nerve preparation and in vitro model of ischemia. 1695 26

Animal studies have shown that noxious inputs onto gamma-motoneurons can cause an increase in the activity of muscle spindles, and it has been proposed that this causes a fusimotor-driven increase in muscle stiffness that is believed to underlie many chronic pain syndromes. To test whether experimental pain also acts on the fusimotor system in humans, unitary recordings were made from 19 spindle afferents (12 Ia, 7 II) located in the ankle and toe extensors or peronei muscles of awake human subjects. Muscle pain was induced by bolus intramuscular injection of 0.5 ml 5% hypertonic saline into tibialis anterior (TA); skin pain was induced by 0.2 ml injection into the overlying skin. Changes in fusimotor drive to the muscle spindles were inferred from changes in the mean discharge frequency and discharge variability of spindle endings in relaxed muscle. During muscle pain no afferents increased their discharge activity: seven afferents (5 Ia, 2 II) showed a decrease and six (4 Ia, 2 II) afferents were not affected. During skin pain of 13 afferents discharge rate increased in one (Ia) and decreased in two (1 Ia, 1 II). On average, the overall discharge rate decreased during muscle pain by 6.1% (P < 0.05; Wilcoxon), but remained essentially the same during skin pain. There was no detectable correlation between subjective pain level and the small change in discharge rate of muscle spindles. Irrespective of the type of pain, discharge variability parameters were not influenced (P > 0.05; Wilcoxon). We conclude that, contrary to the 'vicious cycle' hypothesis, acute activation of muscle or skin nociceptors does not cause a reflex increase in fusimotor drive in humans. Rather, our results are more aligned with the pain adaptation model, based on clinical studies predicting pain-induced reductions of agonist muscle activity.
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PMID:The effects of experimental muscle and skin pain on the static stretch sensitivity of human muscle spindles in relaxed leg muscles. 1840 22

Reflex sympathetic dystrophy (RSD) is a disease of the extremities that can be elicited by different factors, occurring at different sites (e.g., trauma, herpes zoster, myocardial infarction). Independently of its etiology, however, the clinical symptoms of RSD are found most often in distal parts of the extremities affected (hand or foot). In a generalized distribution pattern, the following signs, representing a triad of autonomic, motoric and sensory disturbances, are commonly observed in these regions: 1. dysregulation of blood flow to the skin and of sweating, together with diffuse swelling, 2. impairment of movement and muscular strength; 3. diffuse sensory skin disturbances and spontaneous pain of ariable character (e.g., burning, throbbing, aching, shooting). Pain sensation is generally diffuse; in most cases it is deep and less often, superficial (probably representing bone or skin pain, respectively). This triad occurs at the very onset of RSD. If the distribution pattern is generalized, it can be used as a diagnostic criterion for RSD. Our experimental results support the idea of disturbances of skin blood flow related to abnormal vasoconstrictor outflow. This assumption is primarily based on two observations: 1. 73% of 97 RSD patients (upper extremity affected) showed systematic side differences in fingertip temperatures at room temperature. All points measured on the affected side had higher (n=51) or lower (n= 20) temperature values than corresponding sites on the healthy extremity. Such systematic side differences were found only in 16% out of 79 healthy subjects (p</=0.0001). 2. Whole-body cooling, hands excluded, induced abnormal changes in skin blood flow of the hands affected (e.g., faster or slower decrease in blood flow on the affected side compared to the healthy extremity). This generally leads to higher mean side differences in skin temperature during the whole cooling period in 38 RSD patients as compared with 18 healthy subjects (2.5 degrees vs 0.9 degrees C,p</=0.001). Such abnormalities of skin blood flow were found in the whole distal extremity, independent of the factor eliciting RSD (e.g. proximal or distal trauma, partial nerve lesion). In most cases the predominant symptoms of RSD are swelling of a distal extremity and spontaneous pain. It is presumed that these symptoms are primarily initiated by a noxious event, which can be recognized as a common factor in the history of the disease preceding RSD in most cases. Nociceptor impulses during this event may induce disturbances of sympathetic vasoconstrictor outflow via reflex mechanisms. Most relevant to these symptoms is the hypothesized imbalance between activity (tone) of vasoconstrictor neurons supplying arteries (AVT) and those supplying veins (VVT). If VVT becomes higher than AVT, venous return is impaired, capillary pressure increases, and edema results. Disturbed micromilieu and increased local pressure lead finally to excitation of nociceptors in the tissues affected (e.g., skin and bones). This excitation, in turn, maintains the abnormal vasoconstrictor outflow via reflex mechanisms, thus initiating a vicious circle. Sympatholytic therapy can interrupt the abnormal vasoconstrictor outflow, leading to increased venous return and reducing interstitial pressure and nociceptor activation (interruption of the vicious circle). If sympatholytic therapy is applied early, full recovery may occur.
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PMID:[Development and therapy of the pain syndrome of reflex sympathetic dystrophy. Clinical expression, experimental investigations, and new pathophysiological considerations.]. 1841 24

Activity in both muscle spindle endings and cutaneous stretch receptors contributes to the sensation of joint movement. The present experiments assessed whether muscle pain and subcutaneous pain distort proprioception in humans. The ability to detect the direction of passive movements at the interphalangeal joint of the thumb was measured when pain was induced experimentally in four sites: the flexor pollicis longus (FPL), the subcutaneous tissue overlying this muscle, the flexor carpi radialis (FCR) muscle and the subcutaneous tissue distal to the metacarpophalangeal joint of thumb. Tests were conducted when pain was at a similar subjective intensity. There was no significant difference in the ability to detect flexion or extension under any painful or non-painful condition. The detection of movement was significantly impaired when pain was induced in the FPL muscle, but pain in the FCR, a nearby muscle that does not act on the thumb, had no effect. Subcutaneous pain also significantly impaired movement detection when initiated in skin overlying the thumb, but not in skin overlying the FPL muscle in the forearm. These findings suggest that while both muscle and skin pain can disturb the detection of the direction of movement, the impairment is site-specific and involves regions and tissues that have a proprioceptive role at the joint. Also, pain induced in FPL did not significantly increase the perceived size of the thumb. Proprioceptive mechanisms signalling perceived body size are less disturbed by a relevant muscle nociceptive input than those subserving movement detection. The results highlight the complex relationship between nociceptive inputs and their influence on proprioception and motor control.
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PMID:Local subcutaneous and muscle pain impairs detection of passive movements at the human thumb. 1846 66


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