Lack of pressure pain modulation by heterotopic noxious conditioning stimulation in patients with painful osteoarthritis before, but not following, surgical pain relief

To investigate the influence of chronic nociceptive pain on endogenous pain modulation, the effect of heterotopic noxious conditioning stimulation (HNCS) on perception of various somatosensory modalities was assessed in 15 patients with painful osteoarthritis of the hip. Thirteen patients were re-assessed when pain-free 6-14 months following surgery. Sex- and age matched healthy subjects assessed at similar time intervals served as controls. The effects of HNCS were tested using the upper extremity submaximal effort tourniquet test. Subjects rated tourniquet-induced pain intensity on a visual analogue scale (VAS). Quantitative sensory testing (QST) was performed contralaterally to the maximally painful area in 13 patients and contralaterally to the second most painful area in two patients (i.e. lateral thigh n = 12, frontal thigh n = 1, lateral calf n = 2). Sensibility was assessed before, during and 45 min following the tourniquet test. Perception thresholds to light touch were assessed using von Frey filaments and pressure pain thresholds by pressure algometry. Perception thresholds to non-painful and painful warmth and cold were determined using a Thermotest. In both sessions, patients rated the tourniquet-induced pain higher than controls at the start (P < 0.003 and P < 0.006, respectively), but not at the end of the tourniquet test. Decreased sensitivity to light touch (P < 0.001) and innocuous cold (P < 0.002) was seen during the tourniquet in patients and controls alike, on both occasions, while perception thresholds to innocuous warmth and heat pain remained unaffected. In the first session, pressure pain thresholds increased during the tourniquet test in controls (P < 0.002), but not in patients. In the second session, pressure pain thresholds increased during the tourniquet test in controls (P < 0.001) and in patients (P < 0.02). In conclusion, no pressure pain modulation was induced by HNCS in patients before surgery, as opposed to controls, suggesting a dysfunction in systems subserving 'diffuse noxious inhibitory controls' (DNIC). Normal pressure pain modulation induced by HNCS was seen when patients were re-assessed in a pain-free state following surgery, indicating that the dysfunction of DNIC had been maintained by chronic nociceptive pain.     

Relationship between pain symptoms and referred sensory and trophic changes in patients with gallbladder pathology

The relationship was investigated between algogenic potential of gallbladder pathology and occurrence/extent of sensory and trophic changes in the referred area. Five groups of subjects were studied, with: symptomatic gallbladder calculosis (3-20 colics); asymptomatic calculosis; symptomatic gallbladder shape abnormality (8-18 colics); asymptomatic shape abnormality; normal gallbladder/no symptoms. At the cystic point (CP) and contralaterally, all underwent measurement of: pain thresholds to electrical stimulation of skin, subcutis and muscle; thickness of subcutis and muscle via ultrasounds. Contralaterally to CP, all thresholds were not significantly different in the five groups. At CP, subcutis and muscle thresholds were significantly lower in symptomatic vs asymptomatic patients and/or normals (0.0001相似文献   

Impairment of pain inhibition in chronic tension-type headache

Evidence has been accumulated suggesting that a dysfunction in pain inhibitory systems, i.e. in 'diffuse noxious inhibitory controls' (DNIC)-like mechanisms, might be-amongst other factors-responsible for the development of anatomically generalized chronic pain like fibromyalgia. The aim of the present study was to look for similar impairments in chronic tension-type headache (CTTH) as a regionally specific pain syndrome. Twenty-nine CTTH patients and 25 age- and sex-matched healthy control subjects participated in the study. After baseline assessment of electrical detection and pain thresholds, tonic heat stimuli were concurrently applied by a thermode to the thigh to induce DNIC-like pain inhibition. Tonic heat stimuli were applied either slightly above ('pain' condition) or slightly below ('heat' condition) pain threshold. For determination of electrical detection and pain thresholds, electrocutaneous stimuli were administered either to the forearm (extra-cranial site) or to the temple (cranial site), using a multiple staircase procedure. The increase in the electrical detection and pain thresholds induced by concurrent tonic heat stimulation was significantly smaller in the CTTH patients than in the control subjects. This group difference was present during the 'pain' as well as the 'heat' condition. Furthermore, the electrical detection and pain thresholds were affected in this group-specific manner both at the forearm and at the temple. These findings suggest that patients with CTTH suffer from deficient DNIC-like pain inhibitory mechanisms in a similar manner, as do patients with anatomically generalized chronic pain like fibromyalgia.     

Reactivity to superficial and deep stimuli in patients with chronic musculoskeletal pain

In this study, we evaluated pain sensitivity in patients with fibromyalgia or other types of chronic, diffuse musculoskeletal pain to establish whether fibromyalgia represents the end of a continuum of dysfunction in the nociceptive system. One hundred and forty five patients and 22 healthy subjects (HS) completed an epidemiological questionnaire to provide information about fatigue, stiffness, sleep, the intensity of pain (VAS 0–100) and its extent both at onset and at present. Algometry was performed at all American College of Rheumatology (ACR) tender points and at ten control points. Patients were divided into five main groups: fibromyalgia (FS) patients, secondary-concomitant fibromyalgia (SCFS) patients, patients with widespread pain (WP) but not reaching the ACR criterion of 11 tender points, patients with diffuse multiregional pain (MP) not reaching the ACR criteria (widespread pain, tender point counts), and patients with multiregional pain associated with at least 11 tender points (MPTE). von Frey monofilaments were used to assess superficial punctate pressure pain thresholds. Heat and cold pain thresholds were determined with a thermal stimulator. Ischemic pain was assessed by the cold pressure test and the submaximal effort tourniquet test. The scores for stiffness and present pain intensity gradually increased concomitantly with the increase in tender point count and pain extent. The pressure pain thresholds for positive tender and positive control points were significantly lower in the SCFS, FS and MPTE groups than in HS, MP and WP groups, the latter three groups displaying similar values. In all groups, there were no differences in pain thresholds between positive tender and positive control points. The heat pain threshold and the pain threshold in the cold pressure test were lower in the FS and SCFS groups than in HS. The cold pressure tolerance was lower in patients with widespread pain than in HS. In the von Frey test, all patient groups except MP had similar values, which were significantly lower than in HS. Finally, all patient groups displayed lower tourniquet tolerance than HS. In each psychophysical test, patients with widespread pain and patients with multiregional pain showed similar thresholds; however, the thresholds in the MP or MPTE groups differed from those in the FS and SCFS groups. In the FS group, pain thresholds and pain tolerance did not differ according to the presence of ongoing pain at the stimulated site and were not correlated to ongoing pain. The results indicate that dysfunction in the nociceptive system is already present in patients with multiregional pain with a low tender point count; it becomes more and more severe as the positive tender point count and pain extent increase and it is maximal in fibromyalgia patients.     

A comparison of diffuse noxious inhibitory controls in men and women.

Results from clinical and experimental pain studies provide consistent evidence of sex differences in pain perception, with women reporting more clinical pain and demonstrating lower pain threshold and tolerance levels than men. The present study was designed to assess the notion that sex differences in pain perception may be related to differential activation of supraspinal pain modulation systems. Specifically, the phenomenon of diffuse noxious inhibitory controls (DNIC) was examined in healthy young adult men (n = 39) and women (n = 44) using repeated assessment of nociceptive flexion reflex activity before, during and after exposure to forearm ischemia. Consistent with previous research, women exhibited significantly lower nociceptive flexion reflex thresholds than men, and reported significantly greater pain in response to both forearm ischemia and repeated electrocutaneous stimulation required to elicit the nociceptive flexion reflex. Application of forearm ischemia was associated with a significant decrease in nociceptive flexion reflex activity in both men and women, however, the degree of attenuation of nociceptive flexion reflex activity was not significantly different between the sexes. These findings suggest that men and women exhibit similar activation of diffuse noxious inhibitory controls, but they do not exclude the possibility of sex differences in other forms of central pain modulation.     

The assessment of radiating low back pain by thermal sensory testing

Low back pain radiating into the legs is a common pain syndrome. However, neurological examination, imaging and electromyographic studies are of limited value for prognosis or therapy. The origin of the pain remains unknown. The aim was to evaluate the potential of thermal sensory testing to serve as a diagnostic tool in 24 patients who had low back pain radiating down the S1 dermatome, compared with 26 pain-free controls. The method of limits was used to detect the thresholds of warm sensation, cold sensation, warm pain and cold pain at the L4, L5 and S1 dermatomes of the symptomatic and the non-symptomatic legs. Thresholds on the asymptomatic leg were similar to values obtained in controls. We found a significantly higher threshold for cold sensation in the S1 dermatome of the symptomatic leg of the patients compared with the controls (p< 0.005). In addition, patients who had abnormal neurological examination (50%) had higher thresholds for cold sensation or cold pain in the three dermatomes tested at the symptomatic leg compared with the non-symptomatic leg. No differences in the thresholds of warm sensation or warm pain were detected. We propose that these findings indicate selective damage to the Adelta fibres which are involved in transmission of cold sensation and pain, presumably by root compression. We found no evidence of involvement of C fibres, which transmit warm sensation and pain. Thermal testing should be considered among the testing modalities that are capable of demonstrating objective findings in patients with radiating low back pain.     

Aging and right-left asymmetry in experimental pain measurement

Verbal psychophysical measurements were performed on 100 subjects, both male and female, aged from 20 to 82 years, to ascertain whether different responses to pain exist between the right and left sides of the body in relation to aging and to different capacities of the cerebral hemispheres to process emotions. A single-phase step current applied to the forearm provided a standard noxious stimulus. Sensory threshold (S), pain threshold (P), and tolerance threshold (T) were measured. The sample set was divided into 2 comparable groups either older or younger than 60 years of age. A common trend was found in both groups: right-side scores were consistently lower than the homologous left-side scores. This difference was significant for all thresholds in elderly subjects but only for the pain threshold in the younger subject group. Two-way ANOVA test of the two group scores did not reveal differences due to sex, but age was an influencing factor for sensory and pain thresholds, higher scores being found in the older subject group. An interpretation of the results embodies hemispheric capacities to process verbal and emotional stimuli.     

Psychologic factors are related to some sensory pain thresholds but not nociceptive flexion reflex threshold in chronic whiplash

OBJECTIVES: Sensory hypersensitivity, central hyperexcitability [lowered nociceptive flexion reflex (NFR) thresholds], and psychologic distress are features of chronic whiplash. However, relationships between these substrates are not clear. This study tested the hypothesis that psychologic distress and catastrophization are correlated with sensory hypersensitivity and NFR responses in chronic whiplash. METHODS: Pressure and thermal pain thresholds (mean values across 3 body sites), NFR threshold, and pain at threshold Visual Analog Scale were measured in 30 participants with chronic whiplash and 30 asymptomatic controls. Pain and disability levels Neck Disability Index, psychologic distress (GHQ-28), and catastrophization (PCS) were also measured in the whiplash group. RESULTS: Whiplash injured participants demonstrated lowered pain thresholds to pressure and cold (P<0.05); lowered NFR thresholds (P=0.003), and demonstrated above threshold levels of psychologic distress (GHQ-28) and levels of catastrophization comparable with other musculoskeletal conditions. There were no group differences for heat pain thresholds or pain at NFR threshold. In the whiplash group, PCS scores correlated moderately with cold pain threshold (r=0.51, P=0.01). In contrast, there were no significant correlations between GHQ-28 scores and pain threshold measures or between psychologic factors and NFR responses in whiplash participants. There were no significant correlations between psychologic factors and pain thresholds or NFR responses in controls. DISCUSSION: We have demonstrated that psychologic factors have some association with sensory hypersensitivity (cold pain threshold measures) in chronic whiplash but do not seem to influence spinal cord excitability. This suggests that psychologic disorders are important, but not the only, determinants of central hypersensitivity in whiplash patients.     

Tactual sensitivity of chronic pain patients to non-painful stimuli

Chronic pain research tends to focus on responses to thresholds, tolerance, and discrimination involving painful stimuli. This investigation, however, examines responses of individuals with chronic pain to non-painful stimuli. Two-point thresholds were obtained from 19 chronic pain patients and 17 pain-free individuals. The chronic pain patients had a significantly higher two-point threshold, 40.3 mm (S.D., 15.0 mm) than that of the control group, which had a two-point threshold of 30.8 mm (S.D., 7.4 mm). The results indicate that chronic pain decreases tactual sensitivity to non-painful stimuli.     

The effect of soft tissue deloading tape on thoracic spine pressure pain thresholds in asymptomatic subjects

The application of tape to deload soft tissue is used in the management of thoracic spine pain. A reported clinical feature of this treatment is reduced tenderness of the spine during postero-anterior mobilizations. A randomized, single blind, placebo controlled, repeated measures design study was employed to investigate the effects of deloading tape on pressure pain threshold measurements at the level of the T7 spinous process in an asymptomatic group of 24 subjects. Pressure pain thresholds were assessed prior to and following the application of deloading tape, placebo sham tape and no-tape control conditions. All subjects received all three conditions in a randomized order on three separate days. Differences between the pre- and post-measurements were used as indicators of change in a subject's pressure pain threshold. No significant change in pressure pain threshold measurements was found between conditions. In summary, this study demonstrated that deloading tape applied to the level of the T7 spinous process did not significantly change pressure pain threshold measurements in asymptomatic subjects, raising the possibility that any pain relieving effect may well be conditional upon pain being present.     

Experimental muscle pain provokes long-lasting alterations of thermal sensitivity in the referred pain area.

This study explores thermal sensitivity and thermal nociception for signs of central sensitization in the area of referred muscle pain. Two groups of 24 healthy subjects (ss) each, and with mean ages of, respectively, 27 and 55 years, were first trained in quantitative sensory testing and pain rating. Then, in a second session, referred pain was evoked by injection of 6% hypertonic saline into the infraspinatus muscle. Cold and warm thresholds, synthetic heat threshold (SHT--evoked by an alternating pattern of adjacent cold and warmth), and thermal pain thresholds were measured within the referred pain area at a rate of 1/20 min for 60-120 min. All ss of both groups experienced referred pain mostly in the upper arm and of medium intensity. Pain lasted for approximately 12min with a shorter duration in the older group (p<0.02). The cold threshold increased significantly (p<0.001), and the warm threshold slightly, after the injection and remained high for the whole observation period (i.e. lower and higher temperatures were necessary to elicit cold and warmth, respectively). Threshold recovery was more delayed in the older age group. Of those 28 ss in whom cold pain threshold could be followed during the whole observation period, 18 ss showed an immediate threshold decrease of average 6 degrees C which outlasted the observation period. Four ss responded with a threshold increase. Heat pain thresholds were not affected in the referred pain area. Average synthetic heat threshold did not change; there were, however, distinct and lasting individual threshold shifts in either direction. Ss with lowered cold pain thresholds or evident threshold shifts for synthetic heat had also higher pain ratings. The results demonstrate that experimental muscle pain can induce long-lasting changes in thermal sensitivity and nociception. The unexpected cold threshold increase may tentatively be explained as an expression of long-term depression. The decrease of cold pain threshold or SHT in subgroups of ss may indicate central sensitization. However, the observed changes in this experiment do not provide an unambiguous indicator for central sensitization which seems to be rather individual and might depend on pain intensity and proneness to express central mechanisms of sensitization. Therefore in clinical pain states the individual pattern of sensory abnormalities has to be analysed and interpreted in addition to the pain parameters to assess central involvement.     

Quantitative sensory studies in complex regional pain syndrome type 1/RSD

OBJECTIVE: Patients with complex regional pain syndrome type I (CRPSD1) may have thermal allodynia after application of a non-noxious thermal stimulus to the affected limb. We measured the warm, cold, heat-evoked pain threshold and the cold-evoked pain threshold in the affected area of 16 control patients and patients with complex regional pain syndrome type 1/RSD to test the hypothesis that allodynia results from an abnormality in sensory physiology. SETTING: A contact thermode was used to apply a constant 1 degrees C/second increasing (warm and heat-evoked pain) or decreasing (cold and cold-evoked pain) thermal stimulus until the patient pressed the response button to show that a temperature change was felt by the patient. Student t test was used to compare thresholds in patients and control patients. RESULTS: The cold-evoked pain threshold in patients with CRPSD1/RSD (p <0.001) was significantly decreased when compared with the thresholds in control patients (i.e., a smaller decrease in temperature was necessary to elicit cold-pain in patients with CRPSD1/RSD than in control patients). The heat-evoked pain threshold in patients with CRPS1/RSD was (p <0.05) decreased significantly when compared with thresholds in control patients. The warm- and cold-detection thresholds in patients with CRPS1/RSD were similar to the thresholds in control patients. CONCLUSIONS: This study suggests that thermal allodynia in patients with CRPS1/RSD results from decreased cold-evoked and heat-evoked pain thresholds. The thermal pain thresholds are reset (decreased) so that non-noxious thermal stimuli are perceived to be pain (allodynia).     

Assessing pain perception using the Painmatcher in patients with whiplash-associated disorders.

OBJECTIVE: To evaluate the Painmatcher, in terms of reliability, and to explore the relationship between pain magnitude matching and pain threshold assessments in patients with whiplash-associated disorders. Also, to investigate gender differences in pain thresholds and explore the correlation between pain-related cognitions and pain threshold. DESIGN: A test-retest study. SUBJECTS: Forty-seven patients with whiplash-associated disorders. METHOD: A visual analogue scale and a Painmatcher (an instrument for comparing pain magnitude) were used to evaluate pain intensity. Pain threshold was assessed using the Painmatcher. Pain-related cognitions were assessed using the Painometer and the Tampa Scale for Kinesiophobia. RESULTS: The Painmatcher demonstrated reliable pain magnitude matching scores, but the pain threshold assessment indicated a systematic disagreement. Women exhibited significantly lower pain thresholds than men (p < 0.01). There was a weak but significant correlation between the pain intensity according to the visual analogue scale and the Painmatcher (r = 0.46) (p < 0.01). There was a significant correlation between the emotional experience of pain and pain threshold (r = -0.33) (p < 0.001), but no significant correlation between fear of movement/(re)injury and pain threshold. CONCLUSION: Measuring pain with the Painmatcher is a reliable method, but may include a possible bias in threshold assessments and seems to be associated with unpleasantness.     

The effect of two sites of high frequency vibration on cutaneous pain threshold

The purpose of this study was to evaluate the effect of two sites of high frequency vibration on experimentally produced pain thresholds. Subjects were assigned to one of two experimental groups. Vibration was applied proximal to the site of pain threshold measurement in one group and distal to the measurement site in the other group. The cutaneous pain threshold was measured at the ulnar aspect of the wrist in both groups prior to, during, and following 5 min of vibration. Subjects were 30 right-handed, Caucasian males with a negative history of upper extremity dysfunction. A repeated measures analysis of variance (ANOVA) was used to analyze the data. There was a significant interaction between vibration site and time of pain threshold measurement. Post hoc analysis of that interaction indicated that a significant difference between experimental groups occurred only during vibration; the distal group values were significantly higher than the proximal group values (P less than 0.03). For the distal group, pain threshold values were significantly higher during vibration than pre vibration and post vibration (P less than 0.05). In the proximal group, there was no significant difference in pain threshold values across the 3 time periods. The results of this study indicate that vibration applied distal to the site of pain can provide temporary analgesia.     

Spinal manual therapy produces rapid onset analgesia in a rodent model

A rapid hypoalgesic effect following spinal manual therapy (SMT) has been demonstrated in humans. Although the characteristics of the pain relief are well described, the mechanisms have remained speculative. The purpose of this suite of studies was to investigate the effects of SMT on pain measures using animal models. This study employed a randomized, controlled design. Study 1: Rats without inflammation were allocated to either a treatment group (n = 6) that received three applications of joint mobilization centrally over L5 or a sham-treated group (n = 6) who received non-specific handling. Pressure pain threshold (PPT) and thermal pain threshold (TPT) were measured before and immediately after each intervention. Results demonstrated significantly increased mechanical nociceptive thresholds in the SMT group (p = 0.01) compared to that of the sham-treated group but no difference for thermal nociceptive thresholds. Study 2: The time course effect of an inflammatory and mechanical response following i.pl injection of inflammatory mediators was investigated to determine the appropriate time period for a treatment intervention. Study 3: The effects of SMT on mechanical nociception were investigated following interplanar injection of inflammatory mediators into the right hind paw of rats as a pain model (n = 6 for both SMT and sham-treated groups). Injection of endogenous metabolites produced significant swelling and flaring as well as increased PPT values following SMT (p < 0.02) compared with controls. These results demonstrate a rapid analgesic response following application of SMT, which has similar characteristics as that seen in both symptomatic and asymptomatic human populations.     

Antenatal women with or without pelvic pain can be characterized by generalized or segmental hypoalgesia in late pregnancy

The aims of the present study were to determine the influence of pregnancy on somatosensory responses in women with or without pelvic/lumbosacral pain. Thirty pregnant women participated and were divided into pain (n = 12) and nonpain (n = 18) groups on the basis of pain complaints and positive pain-provoking tests associated with pelvic or lumbosacral pain during the current pregnancy. In the pain group, 9 reported initial pain in trimester 1, 2 in trimester 2, and 1 in trimester 3. Quantitative sensory testing with pressure pain threshold (PPT), heat pain threshold (HPT), and tactile threshold (TT) was performed once during each of the 3 trimesters at referred pain sites (sacrum, back, and pubis) and no pain control sites (thigh, arm, and sternum). All subjects in the pain group reported back pain, and 91% also had pain at the sacrum and pubis. The pain group exhibited significantly greater pain sensitivity than the nonpain group. The HPT and PPT were higher in trimester 3 as compared to trimesters 1 and 2 (P < .012). The increase in thresholds, or hypoalgesia, was generalized and present at both referred pain and control sites in the pain group. In the nonpain group hypoalgesia was localized to the presumed referred pain sites at the back and sacrum. There were no significant variations in the TT in any trimester. The study demonstrates for the first time that hypoalgesia in late pregnancy is generalized in women with pelvic pain and localized in women without pelvic pain. This suggests that the descending noxious inhibitory system is activated in late pregnancy and is probably more intense and generally activated in women with pelvic pain and only segmentally activated in women without pain.     

Low intensity vagal nerve stimulation lowers human thermal pain thresholds

The effect of vagal nerve stimulation (VNS) on thermal pain sensation was studied in eight subjects who had vagal nerve stimulators surgically implanted for purposes of seizure control. Prior to their involvement in the study, all subjects had the intensity of their VNS (30 Hz, 0.5 ms, 1.0-2.75 mA) adjusted upwards until achieving their desired clinical effect of reduced seizures. Thermal pain thresholds were determined using a Medoc TSA-2001 with a thermode applied to the skin of the forearm. During VNS at settings 100% of those used clinically to control their seizures, subjects showed a statistically significant decrease in their thermal pain threshold of 1.1+/-0.4 degrees C. Acute effects of graded VNS on thermal pain thresholds were determined in seven of the subjects after cessation of chronic VNS. Two thermal threshold measurements were obtained while the subject received sham stimulation (0 mA intensity), during tactile control stimulation and during 30 s of VNS at intensities approximately 33, 66 and 100% of the settings utilized to control their seizures. Tactile control stimulation was provided by electrical stimulation of the skin of the ankle with the intensity adjusted by the patient to match the intensity of any sensations felt in the neck during VNS. Subjects were not aware of the settings employed. Their stimulator was adjusted with each trial and an ascending/descending ordering of intensity was utilized with an inter-trial interval of 2 min. Thermal pain thresholds were significantly decreased in relation to tactile control stimulation at all intensities of VNS tested with the greatest effect occurring at the 66% level. Subjects were also monitored non-invasively and hemodynamic responses to VNS were determined. No significant alterations in hemodynamic variables were observed. The findings of this human study are consistent with experiments in non-human animals which demonstrate a pro-nociceptive effect of low intensity VNS.     

Increased postural stiffness during challenging postural tasks in patients with knee osteoarthritis with high pain sensitization

BackgroundPostural stability is affected in knee osteoarthritis patients who present with pain but the link to pain sensitization is unclear.MethodsPatients with knee osteoarthritis completed the Knee Injury and Osteoarthritis Outcome Score and pressure pain thresholds were assessed bilaterally at the knee, lower leg and forearm prior to standing quietly (1 min) on a force platform in four conditions: Firm surface with open eyes, firm surface with closed eyes, soft surface with open eyes, and soft surface with closed eyes. Pain intensity during standing was assessed via numerical rating scale. Postural stability was assessed by the range, velocity, and standard deviation of the Center of Pressure (CoP) extracted from the force platform. The means of three repeated measures per standing condition were analysed. High-sensitization and low-sensitization groups were defined based on bilateral pressure pain thresholds from leg and arm.FindingsFifty-six patients were included. Compared with the low-sensitization group, the high-sensitization group demonstrated 1) smaller pressure pain thresholds at the knee (P < 0.05) although the Knee Injury and Osteoarthritis Outcome Score and pain intensity were not significantly different between groups, and 2) smaller range of the CoP in the anterior-posterior direction during the soft surface with closed eyes condition (P < 0.05).InterpretationSmaller CoP range suggest that patients with more widespread pain sensitivity have increased postural stiffness compared with the low-sensitization group. The greater stiffness found in high-sensitization patients under sensory restrictions (closed eyes and reduced proprioception) might relate to restricted integration of sensory information due to widespread pain sensitization.     

Influence of estrogen levels on thermal perception, pain thresholds, and pain tolerance: studies on women undergoing in vitro fertilization

We examined the relationship between estrogen and pain in women undergoing in vitro fertilization (IVF). Quantitative sensory tests (QST) were performed twice during the IVF-regimen: once during hormonal down-regulation and once during hormonal up-regulation. A group of healthy men and a group of women using monophasic contraceptives were also examined, to control for session-to-session effects. Among the women undergoing IVF, serum 17β-estradiol levels differed strongly between treatments as expected, and increased from 65.7 (SD = 26) pmol/L during the down-regulation phase, to 5,188 (SD = 2,524) pmol/L during the up-regulation phase. Significant outcomes in the QST were only seen for temperature perception thresholds (1.7 °C versus 2.2 °C; P = .003) and cold pain threshold (11.5 °C versus 14.5 °C; P = .04). A similar change in cold pain threshold was also seen in the 2 control groups, however, and statistical analysis suggested that this change was due to a session-to-session effect rather than being the result of hormonal modulation. Heat pain thresholds, heat tolerance, pressure pain thresholds, and the cold pressor test showed no significant differences between sessions. These data demonstrate that pain perception and pain thresholds in healthy women show little, if any, changes even with major variations in serum estradiol levels. PERSPECTIVE: This study shows that pain perception and tolerance in women undergoing in vitro fertilization do not vary, despite the dramatic changes in 17β-estradiol levels induced by the treatment regimen. The result thus suggests that in humans, contrary to experimental animals, changes in estrogen levels have little influence on pain sensitivity.     

Cold allodynia and hyperalgesia in neuropathic pain: the effect of N-methyl-D-aspartate (NMDA) receptor antagonist ketamine--a double-blind,cross-over comparison with alfentanil and placebo

Cold allodynia and hyperalgesia are frequent clinical findings in patients with neuropathic pain. While there have been several clinical studies showing the involvement of central sensitization mechanisms and N-methyl-D-aspartate (NMDA) receptor activation in mechanical allodynia/hyperalgesia and ongoing pain, the mechanisms of thermal allodynia and hyperalgesia have received less attention. The aim of the present study was to examine the effect of the NMDA-receptor antagonist ketamine on thermal allodynia/hyperalgesia, ongoing pain and mechanical allodynia/hyperalgesia in patients with neuropathic pain (11 patients with post-traumatic neuralgia and one patient with post-herpetic neuralgia). All the patients were known to suffer from severe cold allodynia (cold pain detection threshold (CPDT): 23.8 degrees C, median value). The mu-opioid agonist alfentanil was used as an active control. The study design was double-blind and placebo-controlled and the drugs were administered i.v. (bolus dose and infusion). CPDT in the asymptomatic contralateral area was found to be significantly decreased (cold allodynia) compared to CPDT in site- and age-matched normal controls. Heat pain detection thresholds were found to be normal and no consistent heat hyperalgesia occurred. Alfentanil significantly reduced cold allodynia (by increasing CPDT) in symptomatic area (P=0.0076). Ketamine did not significantly increase the threshold. Significant and marked reductions of hyperalgesia to cold (visual analogue score at threshold value) were seen following both alfentanil (4.5 before, 1.4 after, median value) and ketamine (6.8 before, 0.4 after, median value). Alfentanil and ketamine also significantly reduced ongoing pain and mechanical hyperalgesia. It is concluded that NMDA-receptor mediated central sensitization is involved in cold hyperalgesia, but since CPDT remained unaltered, it is likely that other mechanisms are present.