Brain structural changes in patients with chronic myofascial pain.

BACKGROUND: Myofascial trigger points (MTrPs) are a highly prevalent source of musculoskeletal pain. Prolonged ongoing nociceptive input from MTrPs may lead to maladaptive changes in the central nervous system. It remains, however, unknown whether pain from MTrPs is associated with brain atrophy. In addition, stress, which may contribute to the formation of MTrPs, is also known to affect brain structures. Here, we address whether structural brain changes occur in patients with chronic pain originating from MTrPs and whether such changes are related to pain or stress. METHODS: Voxel-based morphometry was used to compare grey-matter (GM) volumes in 21 chronic pain patients, with MTrPs in the bilateral upper trapezius muscles, with 21 healthy controls. Hyperalgesia was assessed by pressure pain thresholds, and stress was assessed by cortisol levels and anxiety questionnaires. RESULTS: Patients exhibited normal stress levels but lowered pain thresholds. GM atrophy was found in dorsal and ventral prefrontal regions in patients. The GM density of the right dorsolateral prefrontal cortex correlated with pain thresholds in patients, i.e. the more atrophy, the lower pain threshold. GM atrophy was also found in the anterior hippocampus, but the atrophy was neither related to pain nor stress. CONCLUSIONS: Patients with chronic myofascial pain exhibit GM atrophy in regions involved in top-down pain modulation and in processing of negative affect. The relationship between the dorsolateral prefrontal cortex and pain thresholds suggests the presence of pain disinhibition. No evidence was found for the involvement of stress. It remains unclear whether the observed atrophy contributes to the development of the chronic pain state or is caused by the ongoing nociceptive input. SIGNIFICANCE: Chronic myofascial pain, caused by myofascial trigger points, is associated with localized brain atrophy in areas involved in pain processing and modulation, among others. These findings extend previous knowledge about peripheral and spinal changes to the supraspinal level.

Flunarizine versus topiramate for chronic migraine prophylaxis: a randomized trial.

OBJECTIVES: Chronic migraine (CM) is a prevalent and devastating disorder with limited therapeutic options. This study explored the efficacy of 10 mg/d flunarizine for CM prophylaxis as compared with 50 mg/d topiramate. METHODS: We conducted a prospective, randomized, open-label, blinded-endpoint trial. Patients with CM were randomized to flunarizine and topiramate treatment. The primary outcomes assessed were the reductions in the total numbers of headache days and migraine days after 8 weeks of treatment. Secondary outcomes were reductions in the numbers of days of acute abortive medication intake and acute abortive medication tablets taken, and the 50% responder rate. RESULTS: Sixty-two subjects were randomized (n=31/group). Patients treated with flunarizine showed significant reductions in the numbers of total headache days (-4.9 vs -2.3, P=.012) and migraine days (-4.3 vs -1.4, P=.001) compared with those treated with topiramate. Patients treated with flunarizine also showed significant reductions in the numbers of days of acute abortive medication intake (-2.3 vs -0.2, P=.005) and acute abortive medication tablets taken (-4.6 vs -0.5, P=.005) and had a higher 50% responder rate in terms of total headache days (58.6% vs 25.9%, P=.013) and migraine days (75.9% vs 29.6%, P=.001), compared with topiramate-treated patients. Flunarizine was generally well tolerated and had a safety profile comparable to that of topiramate. CONCLUSIONS: Our results suggest that, in an 8-week study, 10 mg/d flunarizine is more effective than 50 mg/d topiramate for CM prophylaxis.

Meta-analysis on brain representation of experimental dental pain.

Functional magnetic resonance imaging (fMRI) has been widely used for investigating the brain representation associated with dental pain evoked by pulpal electrical stimulation. However, because of the heterogeneity of experimental designs and the small sample size of individual studies, the common brain representation regarding dental pain has remained elusive. We used imaging meta-analysis to investigate six dental pain-related fMRI studies (n = 87) and tested 3 hypotheses: (1) Dental pain is associated with the 'core' pain-related network; (2) pain-related brain activation is somatotopically organized in the somatosensory cortex; and (3) dental pain is associated with the cognitive-affective network related to pain. Qualitative and quantitative meta-analyses revealed: (1) common activation of the core pain-related network, including the somatosensory cortex, the insula, and the cingulate cortex; (2) inconsistency in somatotopically organized activation of the primary somatosensory cortex; and (3) common activation in the dorsolateral prefrontal cortex, suggesting a role of re-appraisal and coping in the experience of dental pain. In conclusion, fMRI combined with pulpal stimulation can effectively evoke activity in the pain-related network. The dental pain-related brain representation disclosed the mechanisms of how sensory and cognitive-affective factors shape dental pain, which will help in the development of more effective customized methods for central pain control.

Pain catastrophizing is associated with dental pain in a stressful context.

Pain is associated with anxiety in a dental setting. It has remained unclear how cognitive-affective factors modulate pain and anxiety in a stressful context, such as receiving dental procedures. We hypothesized that both the situational factor (unpredictability about painful stimuli) and the trait factor (pain catastrophizing, i.e., the tendency to interpret pain in negative orientation) account for dental pain. Fifteen healthy participants were recruited to perform an associative learning task. They were asked to learn the pairing between visual cues and the intensity of incoming painful stimuli delivered at the right upper central incisor. Brain activation associated with pain was recorded by functional magnetic resonance imaging (fMRI). The participants reported increased anxiety and pain in the stressful context, where stimuli intensity was not predicted by the preceding cue. The score of the Pain Catastrophizing Scale was positively correlated with the increased pain modulated by unpredictability. Brain activation at the right posterior hippocampus, a region critically related to associative learning of aversive stimuli and context, was correlated with the individual catastrophizing level. Our findings suggest that both the situational factor (unpredictability) and the trait factor (catastrophizing) influence dental pain, highlighting the role of cognitive-affective factors in pain control of dental patients.

Healthy-side dominance of middle- and long-latency neuromagnetic fields in idiopathic sudden sensorineural hearing loss.

Any lesion along the neural axis may induce a subsequent functional reorganization at the level above. The present study used magnetoencephalography to investigate auditory-evoked magnetic fields [a component of the middle-latency auditory evoked fields peaking at approximately 50 ms (P50m) and a component of the long-latency auditory evoked fields peaking at approximately 100 ms (N100m)] on stimulation of both healthy and affected ears in patients with acute unilateral idiopathic sudden sensorineural hearing loss (ISSNHL) of moderate degree in order to elucidate the functional plasticity of the auditory system. Sixteen right-handed, previously untreated adult patients with acute unilateral left (n = 8) or right (n = 8) ISSNHL of moderate degree were studied. Sixteen right-handed healthy volunteers with normal hearing served as control. Auditory neuromagnetic responses, measured by a whole-head 306-channel neuromagnetometer, were detected by monaural tone stimulation applied to affected and healthy ears, respectively, in different sessions. Intragroup and intergroup interhemispheric differences of peak dipole strengths and latencies of P50m and N100m, respectively, to monaural tones were evaluated. Healthy-side amplitude dominance of both P50m and N100m was found in ISSNHL, i.e. contralateral dominance was preserved on affected-ear stimulation but ipsilateral dominance was seen on healthy-ear stimulation. The phenomena could be attributed to the combined contralateral attenuation and ipsilateral enhancement of P50m and N100m activity in response to healthy-ear stimulation. Our findings confirmed that functional modulation can occur within the first few tens of milliseconds of evoked response at the auditory cortex in ISSNHL. The mechanisms of healthy-side dominance might be ascribed to a functional retune of auditory pathways, i.e. conjoined contralateral inhibition and ipsilateral excitation of the auditory pathway in response to healthy-ear stimulation. The effect could be registered in cortical responses.

Contact heat evoked potentials as a valid means to study nociceptive pathways in human subjects.

Contact heat evoked potentials (CHEPs) have been difficult to elicit due to slow temperature rise times. A recently developed heat-foil technology was used to elicit pain and CHEPs. Two groups of subjects were separately stimulated at the left arm with contact heat via one fast-acting (70 degrees C/s) heat-foil thermode. A set of CHEPs was recorded, each at three subjective intensities: warm; slight; and moderate pain. In CHEPs, the 3D topography exhibited four components: T3-T4/N450; Cz/N550; Cz/P750; and Pz/P1000. A vertex topography map was observed in the late Cz/N550-Cz/P750 and parietal topography in the very-late Pz/P1000 components. Consistent statistical values in the peak latencies and amplitudes were noted between consecutive investigations. The correlation between the pain intensity ratings and the major Cz/P750 amplitudes was highly significant in each study. Our validity tests suggested CHEPs to be useful for research and clinical applications in studying human pain activation related to thermal and nociceptive pathways.

Non-painful and painful surface and intramuscular electrical stimulation at the thenar and hypothenar sites: differential cerebral dynamics of early to late latency SEPs.

Little is known about somatosensory evoked potentials (SEPs) from muscle stimulation compared to that from skin stimulation. The current study examined this issue in the full SEP spectrum (0-440 ms). The aims of the study were to (1) establish the dynamics of early to late latency SEPs from intramuscular stimulation in contrast to surface stimulation, (2) compare the effect of non-painful and painful stimuli on SEP latencies and amplitudes of the two methods, and (3) investigate to which extent these results can be shared between the median nerve innervated thenar site and ulnar nerve innervated hypothenar site. Stimuli were delivered (2 Hz) at a non-painful and a painful intensity above or within the thenar and hypothenar muscles of the hand. Maximas of the SEPs were extracted by a combination of global field power and visual inspection of the topographies. Amplitudes and latencies of the maximas were analysed by a two-way ANOVA with repeated measures. In the early phase (0-50 ms) the topographic patterns showed different dynamics between surface and intramuscular stimulation and in the late phase (100- 440 ms) prolonged latencies were found for intramuscular stimulation. Apart from this, similar topographic patterns and time sequences were obtained. Significant higher SEP amplitudes for most of the isolated components (C4'/P25, Fz/N35, C4'/P45, Fc2/N65, P4/P90, T4/N137, F3/P150, Cz/P240-P270) were found with surface stimulation compared to intramuscular stimulation. In contrast to surface stimulation, intramuscular stimulation at a stimulation frequency of 2 Hz did not result in a differentiation in amplitude for any of the isolated components. These results indicate differences in the early and late processing of sensory input from skin and muscle.

Cerebral response to electric stimulation of the colon and abdominal skin in healthy subjects and patients with irritable bowel syndrome.

BACKGROUND: Visceral hyperalgesia may play an important part in the pathophysiology of the irritable bowel syndrome (IBS). We investigated the neuronal afferent pathways in healthy volunteers and IBS patients by recording evoked potentials (EPs) elicited by electrical stimulation of the colon and abdominal skin inside and outside the referred pain area. METHODS: Six healthy subjects and nine IBS patients met the inclusion criteria. Morphology and topography of EPs to painful electrical stimuli were estimated in the rectosigmoid junction and on the skin inside/outside the referred pain areas. RESULTS: The EPs to painful stimuli of the gut showed a shorter latency and a smaller amplitude of the first positive peak (P1) in the IBS group. The controls had a mid-latency frontal positive component after 100 ms, whereas no reliable early activation was seen in the IBS patients. In controls, a single late (>150 ms) positive component was seen, whereas the late component was biphasic in the IBS group. The EPs to painful stimuli of the two skin areas differed in IBS patients, but not in controls. CONCLUSION: Differences in the EPs to electrical painful stimulation of the sigmoid colon and skin inside/outside the experimentally evoked referred pain area were seen comparing healthy subjects and IBS patients. The results indicate altered central nervous system responses.

Dipolar source modeling of somatosensory evoked potentials to painful and nonpainful median nerve stimulation.

Dipolar source modeling might help in clarifying whether somatosensory evoked potentials (SEPs) after electrical stimulation at painful intensity contain any information related to the nociceptive processing. SEPs were recorded after left median nerve stimulation at three different intensities: intense but nonpainful (intensity 2); slightly painful (pain threshold; intensity 4); and moderately painful (intensity 6). Scalp SEPs at intensities 2, 4, and 6 were fitted by a five-dipole model. When the strength modifications of the source activities up to 40 ms were examined across the different stimulus intensities, no significant difference was found. In the later epoch (40-200 ms), a posterior parietal dipole and two bilateral sources probably located in the second somatosensory (SII) areas increased significantly their dipole moments when the stimulus was increased from 2 to 4 and became painful. Since no difference was found when the stimulus intensity was increased from 4 to 6, the observed increase of the dipolar strengths is probably related to a variation of the stimulus quality (nonpainful vs. painful), rather than of the stimulus intensity per se. Our findings lead us to conclude that a large convergence of nociceptive and non-nociceptive afferents probably occurs bilaterally in the SII areas.

Cerebral dynamics of SEPS to non-painful and painful cutaneous electrical stimulation of the thenar and hypothenar.

Early, middle and late latency somatosensory evoked potentials (SEPs) elicited by cutaneous electrical stimulation (painful vs. non-painful) of right and left hands were recorded. The aims were to study (1) if lifelong use of dominant right hand would result in different SEP topographies compared to non-dominant left hand stimulation, (2) if painful and non-painful stimuli resulted in different SEP activation patterns for the different latency components and (3) if these results were consistent between two areas of the hand. Electrical stimuli were applied cutaneously above the thenar and hypothenar muscles of the left and right hand. A two-way repeated measures ANOVA was used to test the effects of laterality and intensity for a given peak amplitude and latency. Statistical results yielded no significant difference in peak amplitude for either thenar and hypothenar between the two hands. In contrast, a significant difference in amplitude was observed for 6 components for each stimulus location when the two intensities were compared. These components were found at early, middle and late latencies. No significant latency shift was observed between the two hands. Only the P30 component showed a significant latency shift for both locations with the painful condition having the shorter latency. Thus, life-long use of the dominant hand does not generate detectable changes in cortical evoked activity to sensory input from the skin above thenar and hypothenar muscles. Several SEP components across the time course (0-400 ms) showed increased amplitude when the stimulus was increased from non-painful to painful intensity.