Hyperalgesia and temporal summation of pain after heat injury in man

Temporal summation of pain occurs when repeated stimuli become increasingly painful in spite of unchanged stimulus intensity. Summation can be quantified as the difference in pain between the first and the last stimulus in a train of stimuli. The aim of the study was to compare temporal summation of pain in normal skin with summation of pain in skin with primary and secondary hyperalgesia evoked by a heat injury. A heat injury was produced on the crus of 12 volunteers with a 50×25 mm thermode (47°C, 7 min). Measurements were made before, and 0, 1, 2, and 4 h after the heat injury, in three areas: primary and secondary mechanical hyperalgesia induced by the heat injury, and in a mirror image of the injury on the opposite leg. Temporal summation of pain was induced by repeated electrical stimuli (five stimuli at 2 Hz) and assessed by visual analog scale (VAS). Primary hyperalgesia was evaluated by von Frey hairs and electrical stimuli, and the areas of secondary hyperalgesia with a rigid von Frey hair (314 mN). Significant primary (P<0.000001) and secondary (P<0.00006) mechanical hyperalgesia were evoked by the heat injury. The pain threshold to single electrical stimuli was reduced within the injury (P<0.03), but not outside. The pain responses to single and repeated electrical stimuli were not significantly altered by the injury. Temporal summation of pain occurred in 418 stimulus trains out of 576 (73%), but no significant changes in summation developed in skin with primary or secondary mechanical hyperalgesia compared with normal skin (baseline measurements). Temporal summation at high stimulus intensities was more pronounced than at lower intensities (P<0.0002). We found no correlation between either temporal summation and area of secondary hyperalgesia, or temporal summation and pain intensity during the induction of heat injury. We conclude that the development of primary and secondary mechanical hyperalgesia after heat injury in man was not associated with changes in temporal summation of painful electrical stimuli.     

Vulvar vestibulitis severity--assessment by sensory and pain testing modalities

Vulvar vestibulitis syndrome (VVS) is a common cause of dyspareunia in pre-menopausal women. Previous quantitative sensory test (QST) studies have demonstrated reduced vestibular pain thresholds in these patients. Here we try to find whether QST findings correlate to disease severity. Thirty-five vestibulitis patients, 17 with moderate and 18 with severe disorder, were compared to 22 age matched control women. Tactile and pain thresholds for mechanical pressure and thermal pain were measured at the posterior fourcette. Magnitude estimation of supra-threshold painful stimuli were obtained for mechanical and thermal stimuli, the latter were of tonic and phasic types. Pain thresholds were lower and supra-threshold magnitude estimations were higher in VVS patients, in agreement with disease severity. Cut-off points were defined for results of each test, discriminating between moderate VVS, severe VVS and healthy controls, and allowing calculation of sensitivity and specificity of the various tests. Our findings show that the best discriminative test was mechanical pain threshold obtained by a simple custom made 'spring pressure device'. This test had the highest kappa value (0.82), predicting correctly 88% of all VVS cases and 100% of the severe VVS cases. Supra-threshold pain magnitude estimation for tonic heat stimulation also had a high kappa value (0.73) predicting correctly 82% overall with a 100% correct diagnosis of the control group. QST techniques, both threshold and supra-threshold measurements, seem to be capable of discriminating level of severity of this clinical pain syndrome.     

Reflex receptive fields are enlarged in patients with musculoskeletal low back and neck pain

Pain hypersensitivity has been consistently detected in chronic pain conditions, but the underlying mechanisms are difficult to investigate in humans and thus poorly understood. Patients with endometriosis pain display enlarged reflex receptive fields (RRF), providing a new perspective in the identification of possible mechanisms behind hypersensitivity states in humans. The primary hypothesis of this study was that RRF are enlarged in patients with musculoskeletal pain. Secondary study end points were subjective pain thresholds and nociceptive withdrawal reflex (NWR) thresholds after single and repeated (temporal summation) electrical stimulation. Forty chronic neck pain patients, 40 chronic low back pain patients, and 24 acute low back pain patients were tested. Electrical stimuli were applied to 10 sites on the sole of the foot to quantify the RRF, defined as the area of the foot from where a reflex was evoked. For the secondary end points, electrical stimuli were applied to the cutaneous innervation area of the sural nerve. All patient groups presented enlarged RRF areas compared to pain-free volunteers (P < .001). Moreover, they also displayed lower NWR and pain thresholds to single and repeated electrical stimulation (P < .001). These results demonstrate that musculoskeletal pain conditions are characterized by enlarged RRF, lowered NWR and pain thresholds, and facilitated temporal summation, most likely caused by widespread spinal hyperexcitability. This study contributes to a better understanding of the mechanisms underlying these pain conditions, and it supports the use of the RRF and NWR as objective biomarkers for pain hypersensitivity in clinical and experimental pain research.     

The effect of venlafaxine on ongoing and experimentally induced pain in neuropathic pain patients: a double blind, placebo controlled study.

BACKGROUND AND AIM: The aim of this randomized double blind placebo controlled study was to investigate the effectiveness and the safety of venlafaxine XR 75 and 150 mg on ongoing pain and on quantitative sensory tests in 60 patients with neuropathic pain for 8 weeks. METHODS: Evaluation parameters consisted of ongoing pain intensity (VAS), patient satisfaction, side effects, global efficacy and tolerance. Quantitative sensory measurements taken from the affected area before and after the drug treatment included pin-prick hyperalgesia, allodynia, detection and pain thresholds to electrical and heat stimuli, temporal summation of repetitive electrical and heat stimuli. RESULTS: A total of 55 patients completed the study. VAS scores decreased significantly compared to the baseline measurements in all groups. There was no significant difference between the groups regarding pain intensity and escape medication. The areas of allodynia and pin-prick hyperalgesia decreased significantly in venlafaxine groups compared to the placebo. There was no significant difference between the groups regarding the detection thresholds (electrical and heat). The pain threshold and the summation threshold to electrical stimuli and the summation threshold to heat stimuli increased significantly following treatment in both venlafaxine groups. In addition, the degree of the temporal summation to electrical and heat stimuli decreased significantly following treatment in both venlafaxine groups compared to the placebo. CONCLUSION: The study showed significant effect of venlafaxine in the manifestations of hyperalgesia and temporal summation, but not on the ongoing pain intensity. Furthermore, the quantitative sensory tests provided complementing information to the clinical measures.     

Generalized expansion of nociceptive reflex receptive fields in chronic pain patients

Widespread central hypersensitivity is present in chronic pain and contributes to pain and disability. According to animal studies, expansion of receptive fields of spinal cord neurons is involved in central hypersensitivity. We recently developed a method to quantify nociceptive receptive fields in humans using spinal withdrawal reflexes. Here we hypothesized that patients with chronic pelvic pain display enlarged reflex receptive fields. Secondary endpoints were subjective pain thresholds and nociceptive withdrawal reflex thresholds after single and repeated (temporal summation) electrical stimulation. 20 patients and 25 pain-free subjects were tested. Electrical stimuli were applied to 10 sites on the foot sole for evoking reflexes in the tibialis anterior muscle. The reflex receptive field was defined as the area of the foot (fraction of the foot sole) from which a muscle contraction was evoked. For the secondary endpoints, the stimuli were applied to the cutaneous innervation area of the sural nerve. Medians (25-75 percentiles) of fraction of the foot sole in patients and controls were 0.48 (0.38-0.54) and 0.33 (0.27-0.39), respectively (P = 0.008). Pain and reflex thresholds after sural nerve stimulation were significantly lower in patients than in controls (P < 0.001 for all measurements). This study provides for the first time evidence for widespread expansion of reflex receptive fields in chronic pain patients. It thereby identifies a mechanism involved in central hypersensitivity in human chronic pain. Reverting the expansion of nociceptive receptive fields and exploring the prognostic meaning of this phenomenon may become future targets of clinical research.     

Gender differences in temporal summation of mechanically evoked pain

Several studies indicate that females are more sensitive to experimentally induced pain than males. Moreover, it was recently shown that temporal summation of heat pain is greater in females than males, suggesting that central processing of nociceptive input may be upregulated in women. Temporal summation of pain has been examined principally using thermal or electrical stimuli. The purpose of this study was to investigate the temporal summation to noxious mechanical stimulation, and examine gender differences in temporal summation of mechanically evoked pain. A sharp probe was used to apply brief mechanical stimuli on the fingers of ten healthy females and ten healthy males. Trains of ten repetitive stimuli were applied at an intensity of 1.2-1.3 x the individual subject's pain threshold, at interstimulus intervals (ISIs) ranging from 1 to 6 s. The same or different skin sites were stimulated in any single train of stimuli. The pain ratings for the fifth as well as the tenth stimulus were significantly higher than those for the first stimulus. Also, the pain responses for the tenth stimulus were higher than those for the fifth. There was no overall gender difference in pain ratings, however, there was a significant trial # x gender interaction. Males and females provided comparable magnitude estimates for the first stimulus in the train, but females provided higher pain ratings than males for the fifth as well as the tenth stimulus. Temporal summation occurred across all ISIs, but shorter ISIs (1-3 s) elicited significantly greater temporal summation than longer ISIs (4-6 s). Finally, although higher pain ratings were obtained when the ten consecutive stimuli were applied on the same versus different skin areas, the degree of temporal summation was not significantly different. These findings indicate that temporal summation of mechanically evoked pain is higher in females compared to males, is stimulation frequency dependent and is centrally mediated.     

Psychophysical observations on patients with neuropathic pain relieved by a sympathetic block

Patients with sympathetically maintained pain (SMP) were tested with noxious heat pulses, innocuous mechanical stimuli, and transcutaneous electrical nerve stimulation before and during local anesthetic sympathetic blocks that relieved their pain. The perceived intensity of the pain evoked by these stimuli was measured by the patients' responses on a visual analog scale and compared to the responses obtained when the same stimuli were applied to contralateral normal skin. In 5 of 7 patients tested, graded noxious heat stimuli (43-51 degrees C) applied to painful skin resulted in heat-pain intensity ratings that were essentially identical to the responses obtained when the same stimuli were applied to the normal side. Of the remaining two patients, one was clearly hypoalgesic for heat-pain and the other was probably hyperalgesic. The normal and subnormal heat-evoked responses obtained from abnormal skin were unchanged during completely successful sympathetic blocks. Trains of noxious heat pulses (52 degrees C) evoked summation of the second pain sensation in each of the 4 patients tested. This summation effect was normal and unaffected by a sympathetic block. Four of the patients had allodynia evoked by mechanical stimulation. In each of the 3 allodynia cases tested, transcutaneous nerve stimulation at an intensity that was at threshold for detection evoked burning pain and a coexistent sensation of tingle, indicating that both sensations were due to the activation of A beta axons. Patients without touch-evoked pain reported that electrical stimuli at threshold for detection produced only the sensation of tingle. The pains evoked by touch and by threshold-strength nerve stimulation were eliminated during sympathetic block. In patients with allodynia, trains of gentle mechanical stimuli and trains of threshold-strength electrical nerve stimuli produced summation of the intensity of the burning pain sensation when the stimuli were presented at 0.3 Hz. These results add to a growing body of evidence indicating that the touch-evoked pain of some patients is due to abnormal central activity evoked by input from A beta low-threshold mechanoreceptors. The coexistence of A beta-evoked pain with normal heat-evoked pain and normal heat-pain summation suggests that the central abnormality cannot be a simple hypersensitivity of wide-dynamic-range neurons. The effect of sympathetic blockade on A beta-evoked pain and its summation suggests that the crucial sympathetic interaction may take place centrally. The results show that there is considerable heterogeneity of sensory abnormalities among patients with SMP.(ABSTRACT TRUNCATED AT 400 WORDS)     

Ketamine reduces muscle pain, temporal summation, and referred pain in fibromyalgia patients

Central mechanisms related to referred muscle pain and temporal summation of muscular nociceptive activity are facilitated in fibromyalgia syndrome (FMS) patients. The present study assessed the effects of an NMDA-antagonist (ketamine) on these central mechanisms. FMS patients received either i.v. placebo or ketamine (0.3 mg/kg, Ketalar((R))50% decrease in pain intensity at rest by active drug on two consecutive VAS assessments). Fifteen out of 17 ketamine-responders were included in the second part of the study. Before and after ketamine or placebo, experimental local and referred pain was induced by intramuscular (i.m.) infusion of hypertonic saline (0.7 ml, 5%) into the tibialis anterior (TA) muscle. The saline-induced pain intensity was assessed on an electronic VAS, and the distribution of pain drawn by the subject. In addition, the pain threshold (PT) to i.m. electrical stimulation was determined for single stimulus and five repeated (2 Hz, temporal summation) stimuli. The pressure PT of the TA muscle was determined, and the pressure PT and pressure pain tolerance threshold were determined at three bilaterally located tenderpoints (knee, epicondyle, and mid upper trapezius). VAS scores of pain at rest were progressively reduced during ketamine infusion compared with placebo infusion. Pain intensity (area under the VAS curve) to the post-drug infusion of hypertonic saline was reduced by ketamine (-18. 4+/-0.3% of pre-drug VAS area) compared with placebo (29.9+/-18.8%, P<0.02). Local and referred pain areas were reduced by ketamine (-12. 0+/-14.6% of pre-drug pain areas) compared with placebo (126.3+/-83. 2%, P<0.03). Ketamine had no significant effect on the PT to single i.m. electrical stimulation. However, the span between the PT to single and repeated i.m. stimuli was significantly decreased by the ketamine (-42.3+/-15.0% of pre-drug PT) compared with placebo (50. 5+/-49.2%, P<0.03) indicating a predominant effect on temporal summation. Mean pressure pain tolerance from the three paired tenderpoints was increased by ketamine (16.6+/-6.2% of pre-drug thresholds) compared with placebo (-2.3+/-4.9%, P<0.009). The pressure PT at the TA muscle was increased after ketamine (42.4+/-9. 2% of pre-drug PT) compared with placebo (7.0+/-6.6%, P<0.011). The present study showed that mechanisms involved in referred pain, temporal summation, muscular hyperalgesia, and muscle pain at rest were attenuated by the NMDA-antagonist in FMS patients. It suggested a link between central hyperexcitability and the mechanisms for facilitated referred pain and temporal summation in a sub-group of the fibromyalgia syndrome patients. Whether this is specific for FMS patients or a general phenomena in painful musculoskeletal disorders is not known.     

Psychophysical Tests as Predictors of Back Pain Chronicity in Primary Care

If persons at risk of developing chronic pain could be identified early in a pain episode, treatment could be tailored on the basis of risk. Responses to psychophysical tests differ in persons with chronic pain vs pain-free controls and thus appear promising as indicators of susceptibility to chronic pain. In a cohort of 157 patients making their first primary care visit during a back pain episode, we explored the relationships of psychophysical test responses (pressure pain thresholds at low back and thenar sites, cold pressor pain ratings, conditioned pain modulation, and mechanical temporal summation) to baseline measures of pain and psychological distress and assessed whether test responses predicted clinically significant back pain 4 months later. Examiner-standardized pressure pain thresholds were significantly (P < .05) correlated with baseline back pain severity and diffuseness of bodily pain (Pearson correlations = −.21 to −.35). Lower baseline pressure pain thresholds significantly predicted back pain at 4 months (odds ratio [95% confidence interval]: low back, .66 [.44, .96]; thenar, .62 [.40, .92]); however, after controlling for participant age and sex, these associations were no longer significant. Cold pressor pain, conditioned pain modulation, and mechanical temporal summation were not significant predictors of 4-month back pain in either model.     

Psychophysical examination in patients with post-mastectomy pain

Chronic pain, lymphoedema, post-irradiation neuropathy and other symptoms are reported in as many as 75% of women following breast cancer treatment. This study examined pain and sensory abnormalities in women following breast cancer surgery. Sensory tests were carried out on operated and contralateral sides in 15 women with spontaneous pain and sensory abnormalities and 11 pain-free women. Testing included the VAS score of spontaneous pain, detection and pain threshold to thermal and mechanical stimuli, temporal summation to repetitive heat and pinprick stimuli, and assessment of skin blood flow during repetitive brush and pinprick stimulation. Sensory threshold to pinprick and thermal stimuli was significantly higher on the operated side in both groups while pressure pain threshold was significantly lower in pain patients on the operated side compared to the contralateral side. No side to side difference was seen in pressure pain threshold in the pain-free group. Evoked pain intensity to repetitive stimuli at 0.2 and 2.0 Hz was significantly higher on the operated side in pain patients compared to the control area while no such difference was seen in pain-free patients. Cutaneous blood flow measured by laser Doppler (flux) was significantly higher when the skin was tapped at 2.0 Hz on the operated side compared to contralaterally in pain patients, while no side to side difference was seen in pain-free patients. Pinprick-evoked pain was correlated to spontaneous pain but not to flux. Spontaneous pain was not correlated to flux. Sensitization seems to be a feature in breast cancer-operated women with pain, but not in pain-free women.     

Does a regional nerve block change cutaneous perception thresholds outside the anaesthetic area? Implications for the interpretation of diagnostic blocks.

The present study was performed on pain-free subjects and patients to analyse if local anaesthetics (LA) normally used for nerve blocks in the orofacial region resulted in generalised changes in cutaneous somatosensory perception thresholds outside the territory of the primarily blocked nerve. Five subjects received an intra-oral nerve block and 5 patients received epidural anaesthesia, serving as a reference group considering the larger amounts of LA used in this latter type of anaesthesia. No differences (after vs. prior to LA) were detected regarding thresholds to tactile, cold, warmth or heat pain stimuli in skin areas outside the regions directly blocked. This was also true for the difference limens between warm-cold thresholds. Our data do not indicate any generalised influence on tactile, thermal and pain perception thresholds in pain-free subjects.     

Pain sensitivity in pericranial and extracranial regions

Chronic myofascial pain is very common in the general population. The pain is most frequently located in the shoulder and neck regions, and nociceptive input from these regions may play an important role for tension-type headache. The mechanisms leading to the frequent occurrence of muscle pain in the shoulder and neck regions are largely unknown. It is possible that the pain is caused by increased sensitivity of muscle nociceptors or by central sensitization induced by nociceptive input from muscle. The primary aim of the present study was to compare muscle pain sensitivity in the trapezius and anterior tibial muscles. The secondary aim was to investigate whether temporal summation, a clinical correlate of wind-up, is more pronounced in muscle than in skin and, if so, whether such a difference is more pronounced in the trapezius than in the anterior tibial region. Sixteen healthy subjects were included. Pressure-pain thresholds and electrical cutaneous and intramuscular pain thresholds were measured at standard anatomical points in the trapezius and anterior tibial regions. Temporal summation was assessed by repetitive electrical stimulation. Pressure-pain thresholds (P = 0.005) and intramuscular electrical pain thresholds (P = 0.006) were significantly lower in trapezius than in anterior tibial muscle. Temporal summation was present in skin and muscle of both regions (P < 0.001). The degree of temporal summation was significantly higher in muscle than in skin in the trapezius region (P = 0.02), but not in the anterior tibial region (P = 0.47). In conclusion, we found that muscle pain sensitivity was higher in the trapezius than in the anterior tibial muscle. We also demonstrated that temporal summation could be induced in both muscle and skin and, importantly, that temporal summation was significantly more pronounced in muscle than in skin in the trapezius but not in the anterior tibial region. These data may help to explain why chronic muscle pain most frequently is located in the shoulder and neck regions.     

2003 Wolff Award: Possible parasympathetic contributions to peripheral and central sensitization during migraine

BACKGROUND: Neurologic signs of increased parasympathetic outflow to the head often accompany migraine attacks. Because increased parasympathetic outflow to the cranial cavity induces vasodilation of cerebral and meningeal blood vessels, it can enhance plasma protein extravasation and the release of proinflammatory mediators that activate perivascular nociceptors. We recently showed that activation of intracranial perivascular nociceptors induces peripheral and central sensitization along the trigeminovascular pathway and proposed that these sensitizations mediate the intracranial hypersensitivity and the cutaneous allodynia of migraine. METHODS: The present study investigates possible parasympathetic contributions to the generation of peripheral and central sensitization during migraine by applying intranasal lidocaine to reduce cranial parasympathetic outflow through the sphenopalatine ganglion. RESULTS: In the absence of migraine, patients were pain-free, and their skin sensitivity was normal. Their mean baseline pain thresholds were less than 15 degrees C for cold, more than 45 degrees C for heat, and more than 100 g for mechanical pressure. Their mean pain score was 7.5 of 10 (standard deviation, 1.4) during untreated migraine and 3.5 of 10 (standard deviation, 2.4) after the nasal lidocaine-induced sphenopalatine ganglion block (P <.0001). Most patients developed cutaneous allodynia during migraine, and their mean pain thresholds changed to more than 25 degrees C for cold, less than 40 degrees C for heat, and less than 10 g for mechanical pressure. Following the nasal lidocaine administration (sphenopalatine ganglion block), this allodynia remained unchanged in spite of the pain relief. CONCLUSION: These findings suggest that cranial parasympathetic outflow contributes to migraine pain by activating or sensitizing (or both) intracranial nociceptors, and that these events induce parasympathetically independent allodynia by sensitizing the central nociceptive neurons in the spinal trigeminal nucleus.     

The importance of stimulus configuration for temporal summation of first and second pain to repeated heat stimuli

Temporal summation of pain is suggested to be an important factor during various clinical conditions. Controversies exist as to whether temporal summation exists for A8 fibre-mediated first pain. The aim of the present human experimental study was to investigate the importance of stimulus configuration (intensity, interpulse interval, location) for temporal summation of radiant (laser)- and contact-heat-induced pain. Consecutive stimuli were applied to the same or to adjacent skin locations. Both stimulation techniques evoked rapid temperature changes, which is an important parameter for recruitment of specific cutaneous nociceptors (Aδ and C fibres). Psychophysical thresholds and intensity ratings were used to assess the pain evoked by repeated stimuli applied to the hairy skin of nine volunteers. Inter-pulse interval (IPI) and stimulus intensity were important and interrelated parameters for temporal summation of pain. An increase in IPI resulted in a decreased summation, whereas increased stimulus intensity resulted in increased summation. Brief heat pulses evoked both first and second pain, and summation of the different pain qualities was investigated. Taking the latency from stimulation to perception into consideration, we were able to differentiate and find summation of first (A8 fibre-mediated) and second pain (C fibre-mediated). Summation of first pain was more pronounced for high (38°C) than for low (30–32°C) baseline temperature.     

Analysis of stimulus-evoked pain in patients with myofascial temporomandibular pain disorders

The pathophysiological mechanisms of myofascial temporomandibular disorders (TMD) are still under investigation. The hypothesis that TMD pain is caused by a generalized sensitization of higher order neurons in the nociceptive pathways combined with a decreased efficacy of endogenous inhibitory systems has recently gained support in the literature. This study was designed to further investigate the somatosensory sensibility within and outside the craniofacial region. Twenty-two patients fulfilled the research diagnostic criteria for TMD for myofascial pain (Dworkin and LeResche, J Craniomandib Disord Facial Oral Pain 6 (1992) 301) and 21 age- and sex-matched subjects served as a control group. The somatosensory sensibility to a deep tonic input was tested by standardized infusions of hypertonic saline into the masseter and anterior tibialis muscle. Furthermore, pressure pain thresholds (PPTs) and heat pain thresholds (HPTs) were assessed with phasic stimuli at the same sites before and following the infusions. Myofascial TMD patients reported infusion of hypertonic saline to be more painful on 10 cm visual analogue scales (peak pain 8.8 +/- 0.4 cm) than control subjects (6.8 +/- 0.5 cm, t-test: P = 0.003) in the masseter but not in the anterior tibialis (7.4 +/- 0.5 vs. 6.6 +/- 0.5 cm, P=0.181). The perceived area of experimental masseter pain measured on drawings was marginally larger in TMD patients (2.6+/-0.5 arbitrary units (a.u.)) than in control subjects (1.4 +/- 0.2 a.u., Mann-Whitney: P = 0.048) but no differences were observed for the anterior tibialis (P = 0.771). The PPTs were lower in the myofascial TMD patients compared to the control group, both in the masseter (analysis of variance (ANOVA): P = 0.002) and in the anterior tibialis (P = 0.005), whereas there were no significant differences in HPT (ANOVAs: P = 0.357, P = 0.101). There were no significant correlations between measures of somatosensory sensibility and measures of clinical pain intensity, pain duration, graded chronic pain scores or somatization or depression scores (Pearson: R < 0.304, P > 0.172). The present study in a well-defined group of myofascial TMD patients found that the responsiveness to both tonic and phasic deep stimuli, but not to phasic superficial inputs at the pain threshold level, in the craniofacial region was higher compared with a control group. These findings suggest that myofascial TMD pain is associated with a facilitation of stimulus-evoked pain primarily, but not exclusively related to the painful region.     

Contribution of myofascial trigger points to migraine symptoms.

This study evaluated the contribution of myofascial trigger points (TrPs) to migraine pain. Seventy-eight migraine patients with cervical active TrPs whose referred areas (RAs) coincided with migraine sites (frontal/temporal) underwent electrical pain threshold measurement in skin, subcutis, and muscle in TrPs and RAs at baseline and after 3, 10, 30, and 60 days; migraine pain assessment (number and intensity of attacks) for 60 days before and 60 days after study start. Fifty-four patients (group 1) underwent TrP anesthetic infiltration on the 3rd, 10th, 30th, and 60th day (after threshold measurement); 24 (group 2) received no treatment. Twenty normal subjects underwent threshold measurements in the same sites and time points as patients. At baseline, all patients showed lower than normal thresholds in TrPs and RAs in all tissues (P < .001). During treatment in group 1, all thresholds increased progressively in TrPs and RAs (P < .0001), with sensory normalization of skin/subcutis in RAs at the end of treatment; migraine pain decreased (P < .001). Threshold increase in RAs and migraine reduction correlated linearly (.0001 < P < .006). In group 2 and normal subjects, no changes occurred. Cervical TrPs with referred areas in migraine sites thus contribute substantially to migraine symptoms, the peripheral nociceptive input from TrPs probably enhancing the sensitization level of central sensory neurons. PERSPECTIVE: This article shows the beneficial effects of local therapy of active myofascial trigger points (TrPs) on migraine symptoms in patients in whom migraine sites coincide with the referred areas of the TrPs. These results suggest that migraine pain is often contributed to by myofascial inputs that enhance the level of central neuronal excitability.     

Selective reduction of second pain sensations by systemic morphine in humans

A variety of forms of painful stimulation were delivered to human subjects in order to determine whether therapeutic dosages of systemic morphine might produce significant attenuation of some forms of phasic pain that are tolerable for experimental usage. Consistent with previous reports, simple application of thermal or electrical energy to the skin (for 3 sec) produced sensations of pain that were not significantly reduced by prior administration of morphine. Similarly, subjects that were trained to focus their attention on the magnitude of the immediate (first) pain sensation evoked by brief electrical or mechanical stimulation did not report reduction by morphine of pain attributed to conduction in myelinated peripheral nociceptors. In contrast, the magnitude of late (second) pain sensations produced by brief pulses of electrical, thermal or mechanical stimuli to the same subjects was consistently reduced significantly by doses of 5 or 10 mg of morphine. The simplest interpretation of the effect on second pain intensity is that morphine preferentially attenuates input from unmyelinated nociceptors. This conclusion was reinforced by an experiment in which chemicals were applied to the skin. Morphine reduced pain produced by capsaicin (presumed to selectively excite unmyelinated peripheral afferents) but did not diminish pain elicited by bradykinin (presumed to excite A delta and C nociceptors). Comparing long duration pains from chemical stimulation (lasting in excess of 5 min) with briefer pains elicited by 50 msec to 3 sec of stimulation did not support the notion that morphine acts selectively on tonic pain. Also, after-sensations that could be discerned following second pain were not eliminated by morphine, and paired pulse facilitation of first pain sensations remained after administration of morphine, indicating that temporal summation is not preferentially reduced. Regardless of duration, frequency or latency, pain arising exclusively from unmyelinated nociceptors was attenuated substantially, but other elicited sensations were not reliably affected. For example, detection thresholds for warmth were unaffected by morphine, demonstrating that input from all unmyelinated afferents is not reduced.     

QTc dispersion and P-wave dispersion during migraine attacks

The aim of this study was to investigate increase of QTc dispersion and P-wave dispersion during migraine attacks. Fifty-five patients (16-65 years of age, 49 women, six men) with migraine were included in our study. Heart rate, QTc interval, maximum and minimum QTc interval, QTc dispersion, maximum and minimum P-wave duration and P-wave dispersion were measured from 12-lead ECG recording during migraine attacks and pain-free periods. ECGs were transferred to a personal computer via a scanner and then used for magnification of x400 by Adobe Photoshop software. Maximum QTc interval (454 +/- 24 ms vs. 429 +/- 23 ms, P < 0.001), QTc interval (443 +/- 26 ms vs. 408 +/- 22 ms, P < 0.001) and QTc dispersion (63 +/- 18 ms vs. 43 +/- 14 ms, P < 0.001) were found significantly higher during migraine attacks compared with pain-free periods. Maximum P-wave duration (107 +/- 11 ms vs. 100 +/- 11 ms, P < 0.001) and P-wave dispersion (45 +/- 13 ms vs. 35 +/- 13 ms, P < 0.001) were found higher during migraine attacks than pain-free periods. We concluded that migraine attacks are associated with increased QTc and P-wave dispersion compared with pain-free periods.     

Age effects on pain thresholds, temporal summation and spatial summation of heat and pressure pain

Experimental data on age-related changes in pain perception have so far been contradictory. It has appeared that the type of pain induction method is critical in this context, with sensitivity to heat pain being decreased whereas sensitivity to pressure pain may be even enhanced in the elderly. Furthermore, it has been shown that temporal summation of heat pain is more pronounced in the elderly but it has remained unclear whether age differences in temporal summation are also evident when using other pain induction methods. No studies on age-related changes in spatial summation of pain have so far been conducted. The aim of the present study was to provide a comprehensive survey on age-related changes in pain perception, i.e. in somatosensory thresholds (warmth, cold, vibration), pain thresholds (heat, pressure) and spatial and temporal summation of heat and pressure pain. We investigated 20 young (mean age 27.1 years) and 20 elderly (mean age 71.6 years) subjects. Our results confirmed and extended previous findings by showing that somatosensory thresholds for non-noxious stimuli increase with age whereas pressure pain thresholds decrease and heat pain thresholds show no age-related changes. Apart from an enhanced temporal summation of heat pain, pain summation was not found to be critically affected by age. The results of the present study provide evidence for stimulus-specific changes in pain perception in the elderly, with deep tissue (muscle) nociception being affected differently by age than superficial tissue (skin) nociception. Summation mechanisms contribute only moderately to age changes in pain perception.