Pain trajectories and neuropathic pain symptoms following lung cancer surgery: A prospective cohort study.

BACKGROUND: Persistent postsurgical pain (PPSP) after lung cancer surgery is common and current definitions are based on evaluations at a single time point after surgery. Pain intensity and symptoms may however fluctuate and change over time, and be impacted by multiple and shifting factors. Studies of postoperative recovery patterns and transition from acute to chronic pain are needed for further investigation of preventive measures and treatments to modify unfavourable recovery paths. METHODS: In this explorative study, 85 patients undergoing surgery due to either presumptive or confirmed lung cancer reported pain intensities bi-monthly for 12 months. Pain trajectories during recovery were investigated, using group-based trajectory modelling. Associations with possible risk factors for PPSP, including clinical variables and anxiety and depression score (HADS), were also explored. RESULTS: A trajectory model containing three 12-month pain recovery groups was computed. One group without PPSP fully recovered (50%) within two to three months. Another group with mild-intensity PPSP followed a protracted recovery trajectory (37%), while incomplete recovery was observed in the last group (13%). Acute postoperative pain and younger age were associated with a less favourable recovery trajectory. More neuropathic pain symptoms were observed in patients with incomplete recovery. CONCLUSIONS: Three clinically relevant recovery trajectories were identified, based on comprehensive pain tracking. Higher acute postoperative pain intensity was associated with an unfavourable pain recovery trajectory. SIGNIFICANCE STATEMENT: Understanding the transition from acute to chronic postoperative pain and identifying preoperative risk factors is essential for the development of targeted treatments and the implementation of preventive measures. This study (1) identified distinct recovery trajectories based on frequent pain assessment follow-ups for 12 months after surgery and (2) evaluated risk factors for unfavourable postoperative pain recovery paths. Findings suggest that early higher postoperative pain intensity is associated with an unfavourable long-term recovery path.

Quantitative sensory testing, psychological profiles and clinical pain in patients with psoriatic arthritis and hand osteoarthritis experiencing pain of at least moderate intensity.

BACKGROUND: Chronic pain is the hallmark symptom of joint diseases. This study examined the differences in quantitative sensory testing between patients with psoriatic arthritis (PsA), hand osteoarthritis (hand-OA) and a pain-free control group and differences between patients with and without concomitant fibromyalgia (cFM). METHODS: All patients and pain-free controls were assessed using pressure pain thresholds (PPT), temporal summation of pain (TSP), conditioned pain modulation (CPM) and clinical pain intensities. Psychological distress was assessed with the Hospital Anxiety and Depression Scale, Pain Catastrophizing Scale, and Pittsburgh Sleep Quality Index. Disability was assessed with the Health Assessment Questionnaire and pain quality with the painDETECT questionnaire. cFM was identified using the revised 2016 American College of Rheumatology diagnostic criteria. RESULTS: Patients with hand-OA (n = 75) or PsA (n = 58) had statistically significant lower PPTs and CPM, greater TSP, and higher scores of psychological distress (p < 0.05) than controls (n = 20). Patients with cFM (58%) had higher scores of depression (p = 0.001), anxiety (p = 0.004), catastrophizing (p = 0.012), disability (p < 0.001), higher painDETECT score (p = 0.001), TSP (p = 0.027), and reduced sleep quality (p = 0.021) when compared to patients without cFM. CONCLUSION: Patients with hand-OA and PsA exhibited signs of pain sensitization and a higher degree of psychological distress and disability than pain-free individuals. Patients with cFM had greater TSP, painDETECT score, disability, catastrophizing, and reduced sleep quality, than patients without, indicating greater degree of pain sensitization, psychological burden, and disability. STATEMENT OF SIGNIFICANCE: This paper shows that a significant proportion of patients with hand osteoarthritis and psoriatic arthritis with moderate pain intensity have significantly increased signs of pain sensitization and markers of psychological distress. A large proportion of these patients fulfil the criteria for concomitant fibromyalgia and these patients show even greater propensity towards pain sensitization and psychological distress.

Total knee replacement and non-surgical treatment of knee osteoarthritis: 2-year outcome from two parallel randomized controlled trials.

OBJECTIVES: To compare 2-year outcomes of total knee replacement (TKR) followed by non-surgical treatment to that of non-surgical treatment alone and outcomes of the same non-surgical treatment to that of written advice. DESIGN: In two randomized trials, 200 (mean age 66) adults with moderate to severe knee osteoarthritis (OA), 100 eligible for TKR and 100 not eligible for TKR, were randomized to TKR followed by non-surgical treatment, non-surgical treatment alone, or written advice. Non-surgical treatment consisted of 12 weeks of supervised exercise, education, dietary advice, use of insoles, and pain medication. The primary outcome was the mean score of the Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales, covering pain, symptoms, activities of daily living (ADL), and quality of life (QOL). RESULTS: Patients randomized to TKR had greater improvements than patients randomized to non-surgical treatment alone (difference of 18.3 points (95% CI; 11.3 to 25.3)), who in turn improved more than patients randomized to written advice (difference of 7.0 points (95% CI; 0.4 to 13.5)). Among patients eligible for TKR, 16 (32%) from the non-surgical group underwent TKR during 2 years and among those initially ineligible, seven patients (14%) from the non-surgical group and ten (20%) from the written advice group underwent TKR. CONCLUSIONS: TKR followed by non-surgical treatment is more effective on pain and function than non-surgical treatment alone, which in turn is more effective than written advice. Two out of three patients with moderate to severe knee OA eligible for TKR delayed surgery for at least 2 years following non-surgical treatment. TRIAL REGISTRATION: ClinicalTrials.gov numbers NCT01410409 and NCT01535001.

Histaminergic and non-histaminergic elicited itch is attenuated in capsaicin-evoked areas of allodynia and hyperalgesia: A healthy volunteer study.

BACKGROUND: Chronic pain patients with sensitization may exhibit decreased sensitivity to normally pruritogenic sensory stimuli and moreover occasionally perceive these as painful. This study explored the relationship between itch and pain, by evaluating histaminergic and non-histaminergic itch evoked in capsaicin-induced allodynic and hyperalgesic areas. METHODS: In 28 healthy volunteers, capsaicin (100 µg/0.1 mL) was injected intradermally in the volar forearm to establish secondary dysesthesias. After the capsaicin-induced pain subsided, the areas of allodynia and hyperalgesia were mapped and itch was provoked inside these areas by histamine (10 mg/mL) and cowhage (25-40 spicules). The evoked itch and pain were recorded on a visual analogue scale (VAS 0-10 cm). Contralateral injection of 0.1 mL isotonic saline served as a control. RESULTS: Histaminergic and non-histaminergic evoked itch were significantly decreased when provoked in allodynic skin (p < 0.05). The area-under-the-curve of the evoked itch was reduced -43% from 18.0 ± 2.6 cm10 min in normal skin to 10.3 ± 1.8 cm10 min in allodynic skin (p < 0.01) for cowhage and -56% from 20.0 ± 3.5 cm10 min in normal skin to 8.8 ± 2.3 cm10 min allodynic skin (p < 0.001) for histamine. The pain responses to the pruritogens were not significantly altered between the areas of allodynia and normal skin (p > 0.1). An additional experiment showed that pinprick hyperalgesia in the absence of allodynia was sufficient to evoke the observed reduced sensitivity to itch stimuli. CONCLUSIONS: Cutaneous sensitization (secondary allodynia and hyperalgesia) reduced itch responses regardless of the type of itch model applied and without attenuation of the associated pruritogen-induced pain responses. This could explain the decreased sensitivity to itch provocations previously observed in patients with chronic pain. SIGNIFICANCE: This study shows that the neuronal sensitization processes underlying the development secondary hyperalgesia involve significant gating of histaminergic as well as non-histaminergic pruriceptive transmission. Because these itch provocations normally target specific subpopulations of C-nociceptors they could be of relevance for exploratory purposes in pain patients.

The interaction between NGF-induced hyperalgesia and acid-provoked pain in the infrapatellar fat pad and tibialis anterior muscle of healthy volunteers.

BACKGROUND: Tissue pH is lowered in inflamed tissues, and the increased proton concentration activates acid-sensing ion channels (ASICs), contributing to pain and hyperalgesia. ASICs can be upregulated by nerve growth factor (NGF). The aim of this study was to investigate two new human experimental pain models combining NGF- and acid-induced pain in a randomized, controlled, double-blind study. METHODS: In experiment 1, volunteers (N = 16) received an injection of either NGF or isotonic saline in each infrapatellar fat pad (IFP). One day after 5 mL of phosphate-buffered acidic saline was infused into each IFP at a rate of 20 mL/h. In experiment 2, the tibialis anterior (TA) muscle of additional volunteers (N = 16) was examined, following the same procedure except that the volume and infusion rate of acid were different (10 mL, 30 mL/h). Continuous pain ratings were recorded during and after acid infusions. In addition, soreness scores on a Likert scale and pressure pain thresholds (PPTs) were assessed. RESULTS: The PPT of the IFP was significantly decreased at the NGF injection site on day 1, but acid-provoked pain ratings and the change in PPT from pre- to postinfusion between the knees were similar. In the muscle pain model, local mechanical hyperalgesia developed 3 h after the NGF injection and a significant additional decrease in PPT was found after acid infusion compared to preinfusion. CONCLUSIONS: NGF sensitization in the IFP was not facilitated by acid, whereas an acid-provoked enhancement of muscle hyperalgesia was found. NGF sensitization of adipose tissue responds differently to acid provocation compared to muscle tissue. SIGNIFICANCE: Quantification of two novel pain models combining NGF and acid. Hyperalgesia developed after NGF injection in the infrapatellar fat pad, but it was not facilitated by acid provocation. Contrary, NGF-induced hyperalgesia in muscle tissue was enhanced by acid.

Facilitation of pain sensitization in knee osteoarthritis and persistent post-operative pain: a cross-sectional study.

BACKGROUND: Around 20% of patients with osteoarthritis (OA) have chronic post-operative pain after total knee arthroplasty (TKA) and often undergo revision surgery with unfavourable pain outcome. This study compared sensitization in pain patients with knee OA and after revision TKA (re-TKA). METHODS: Median pressure pain thresholds (PPTs) assessed from the most affected knee (localized sensitization) were used to subgroup 53 patients with OA pain and 20 patients with pain after re-TKA: group 1: OA and high-knee PPT; group 2: OA and low-knee PPT; group 3: re-TKA and high-knee PPT; group 4: re-TKA and low-knee PPT. Clinical pain intensity was assessed using a visual analogue scale (VAS). Bilateral PPTs were measured from the lower leg and forearm (spreading sensitization). Furthermore, the pain intensities evoked by 10 repeated pressure pain stimuli (temporal summation) at the knee and lower leg were assessed on an electronic VAS. RESULTS: The mean clinical pain intensity was not significantly different between groups. The PPTs from both lower leg and forearm were significantly lower in group 4 compared to groups 1, 2, and 3 and in groups 2 and 3 compared to group 1 (p < 0.05). Temporal summations from the knee and lower leg were significantly facilitated in groups 3 and 4 compared to groups 1 and 2 (p < 0.05). CONCLUSIONS: Despite similar pain intensities, facilitated temporal summation is worse in re-TKA than in OA and patients with high local knee hyperalgesia show more prominent spreading sensitization. The study suggests that sensitization should be considered in knee OA especially before re-TKA.

Normalization of widespread hyperesthesia and facilitated spatial summation of deep-tissue pain in knee osteoarthritis patients after knee replacement.

OBJECTIVE: The modest association between radiographic joint damage and pain in osteoarthritis (OA) has led to the suggestion of facilitated central pain processing. This study evaluated the importance of ongoing tissue pathology in the maintenance of enhanced central pain processing. METHODS: Pain assessment was performed on 48 patients with symptomatic knee OA and 21 sex- and age-matched pain-free healthy control subjects. Twenty of the OA patients subsequently underwent total knee replacement surgery and were reassessed. Pressure-pain thresholds (PPTs) were recorded using a pressure algometer (both over and distant from the knee) and a double-chamber inflatable cuff mounted around the calf. Spatial summation was assessed by relating PPTs using the dual- and single-chamber cuff. Conditioned pain modulation (CPM) was assessed by recording the increase in PPT in response to experimental arm pain. RESULTS: PPTs at the knee and at sites away from the knee were reduced in OA patients as compared with healthy pain-free control subjects (P < 0.0001). Cuff PPTs were decreased in OA patients as compared with the healthy controls (P < 0.05), who also exhibited a greater degree of spatial summation (P < 0.05). Whereas an elevation of PPTs was noted in the healthy controls in response to experimental arm pain (P < 0.0001), no such CPM was observed in the OA patients. Following joint replacement in the OA patients, there was a reduction in the widespread mechanical hyperesthesia, along with normalization of spatial summation ratios and restoration of CPM. CONCLUSION: The widespread hyperesthesia and enhanced spatial summation observed in OA patients imply sensitized central pain mechanisms together with the loss of CPM. Normalization of the results following joint replacement implies that these central pain processes are maintained by peripheral input.

Descending pain modulation and its interaction with peripheral sensitization following sustained isometric muscle contraction in fibromyalgia.

OBJECTIVE: Sustained isometric muscle contraction (fatiguing contraction) recruits segmental and/or extrasegmental descending inhibition in healthy subjects but not in fibromyalgia (FM). We hypothesized that fatiguing contraction may shift descending pain modulation from inhibition towards facilitation and that the effect of descending pain modulation be dependent on peripheral muscle pain sensitivity. METHODS: Pressure pain thresholds (PPT) were measured from 13 points bilaterally in the upper trapezius muscle and from the mid-point bilaterally in the tibialis anterior before-, immediately after-, and 20 min after fatiguing contraction of shoulder abduction in 22 FM patients and 22 matched healthy controls. Rate of fatigue, pain intensity, and the duration of fatiguing contraction were recorded. RESULTS: The duration of fatiguing contraction was significantly shorter in FM (132.4 ± 25.2 s) than healthy control groups (286.2 ± 24.1 s) (P < 0.05), pain intensity was significantly higher in FM (8.25 ± 0.8 cm) than in healthy controls (5.1 ± 0.65 cm) (P < 0.01), whereas both groups reported similar fatigue intensity (P > 0.05). Following the contraction, PPTs were increased significantly and heterogeneously in the upper trapezius over time, but not, in the tibialis anterior muscle in healthy controls. However, PPT were significantly decreased over time in the tibialis anterior (P < 0.05), but not, in the upper trapezius in FM. CONCLUSIONS: Descending pain modulation shifts from descending inhibition towards descending facilitation following muscle nociception in FM. Peripheral mechanical hyperalgesia and descending facilitation counterbalance the effect of descending inhibition in FM.

Quantitative sensory tests before and 1(1/2) years after orthognathic surgery: a cross-sectional study.

Quality control is very important in relation to invasive and lengthy treatments, such as integrated orthodontic and surgical correction of dentofacial deformities. The aim of this cross-sectional study was to compare self-reported somatosensory disturbances and quantitative sensory testing (QST) findings between two groups of patients and a healthy control group (n = 24); one group (n = 21) scheduled for bimaxillary orthognathic surgery (BOS) (pre-op) and one group (n = 24) examined 1(1/2) years after BOS (post-op). Self-reported data on pain and somatosensory disturbances were collected, and QST was performed at six trigeminal and one extratrigeminal site. Sensitivity to brush stroke, tactile stimuli, pinprick, two-point-discrimination threshold (2P-DT), pinch pain threshold (PiPT) and pressure pain threshold (PPT) was evaluated. Results were analysed with anovas, Spearman's Correlation, and chi square tests. Eight per cent of post-op patients reported intra-oral, 46% extra-oral, and 46% no somatosensory disturbances. Sensitivity to brush stroke, pinprick and 2P-DT was significantly increased at all examination sites in the post-op patients compared with healthy controls (P < 0.002). Tactile thresholds and PPT did not differ between groups (P > 0.071). Pinch pain threshold were decreased in pre-op patients compared with controls (P < 0.040). Self-reported somatosensory disturbances were not correlated with QST findings. In conclusion; 1(1/2) years after BOS, a large proportion of patients reported somatosensory disturbances and was hypersensitive to mechanical stimuli when compared with pre-op patients and healthy controls. Pre-op patients showed minor somatosensory changes. In addition to patients serving as their own control in prospective studies, a healthy control group and extratrigeminal control sites should be included in future studies.

EULAR evidence-based recommendations for the management of fibromyalgia syndrome.

OBJECTIVE: To develop evidence-based recommendations for the management of fibromyalgia syndrome. METHODS: A multidisciplinary task force was formed representing 11 European countries. The design of the study, including search strategy, participants, interventions, outcome measures, data collection and analytical method, was defined at the outset. A systematic review was undertaken with the keywords "fibromyalgia", "treatment or management" and "trial". Studies were excluded if they did not utilise the American College of Rheumatology classification criteria, were not clinical trials, or included patients with chronic fatigue syndrome or myalgic encephalomyelitis. Primary outcome measures were change in pain assessed by visual analogue scale and fibromyalgia impact questionnaire. The quality of the studies was categorised based on randomisation, blinding and allocation concealment. Only the highest quality studies were used to base recommendations on. When there was insufficient evidence from the literature, a Delphi process was used to provide basis for recommendation. RESULTS: 146 studies were eligible for the review. 39 pharmacological intervention studies and 59 non-pharmacological were included in the final recommendation summary tables once those of a lower quality or with insufficient data were separated. The categories of treatment identified were antidepressants, analgesics, and "other pharmacological" and exercise, cognitive behavioural therapy, education, dietary interventions and "other non-pharmacological". In many studies sample size was small and the quality of the study was insufficient for strong recommendations to be made. CONCLUSIONS: Nine recommendations for the management of fibromyalgia syndrome were developed using a systematic review and expert consensus.

Sex-related differences in NMDA-evoked rat masseter muscle afferent discharge result from estrogen-mediated modulation of peripheral NMDA receptor activity.

In the present study, the hypothesis that sex-related differences in glutamate-evoked rat masseter muscle afferent discharge may result from estrogen-related modulation of peripheral N-methyl-d-aspartate (NMDA) receptor activity and/or expression was tested by examining afferent fiber discharge in response to masseter injection of NMDA and the expression of NR2A/B subunits by masseter ganglion neurons in male and female rats. The results showed that injection of NMDA into the masseter muscle evoked discharges in putative mechanonociceptive afferent fibers and increased blood pressure that was concentration-dependent, however, a systemic action of NMDA appeared responsible for increased blood pressure. NMDA-evoked afferent discharge was significantly greater in female than in male rats, was positively correlated with plasma estrogen levels in females and was significantly greater in ovariectomized female rats treated with a high dose (5 mug/day) compared with a low dose (0.5 mug/day) of estrogen. Pre-treatment of high dose estrogen-treated-ovariectomized female rats with the Src tyrosine kinase inhibitor PP2 did not affect NMDA-evoked afferent discharge. NMDA-evoked afferent discharge was attenuated by the antagonists ketamine and ifenprodil, which is selective for NR2B containing NMDA receptors. Fewer masseter ganglion neurons expressed the NR2A (16%) subunit as compared with the NR2B subunit (38%), which was expressed at higher frequencies in intact female (46%) and high dose estrogen-treated ovariectomized female (60%) rats than in male (31%) rats. Taken together, these results suggest that sex-related differences in NMDA-evoked masseter afferent discharge are due, at least in part, to an estrogen-mediated increase in expression of peripheral NMDA receptors by masseter ganglion neurons in female rats.

Sensitivity of rat temporalis muscle afferent fibers to peripheral N-methyl-D-aspartate receptor activation.

The temporalis muscle is a common source of pain in headache and chronic craniofacial pain conditions such as temporomandibular disorders, which have an increased prevalence in women. The characteristics of slowly conducting temporalis afferent fibers have not been investigated. Therefore, the aim of the present study was to examine the characteristics of slowly conducting temporalis muscle afferent fibers and to determine whether these fibers are excited by activation of peripheral N-methyl-D-aspartate receptors. The response properties of a total of 117 temporalis afferent fibers were assessed in male and female rats. A majority of these fibers had high mechanical thresholds and slow conduction velocities (<10 m/s). The mechanical threshold of the temporalis afferent fibers was inversely correlated with afferent conduction velocity, however, no sex-related differences in mechanical threshold were identified. There were also no sex-related differences in N-methyl-D-aspartate-evoked afferent discharge. Indeed, injection of a high concentration (1600 mM) of N-methyl-D-aspartate into the temporalis muscle was necessary to evoke significant afferent discharge. Thirty minutes after the initial injection of N-methyl-D-aspartate into the temporalis muscle, a second injection of N-methyl-D-aspartate produced a response only about 50% as large as the initial injection. Co-injection of ketamine (20 mM) with the second injection of N-methyl-D-aspartate significantly decreased N-methyl-D-aspartate-evoked afferent discharge in both sexes. This concentration of ketamine is greater than that needed to attenuate afferent discharge evoked by injection of glutamate into the masseter muscle. These results suggest that unlike masseter afferent fibers, temporalis afferent fibers are relatively insensitive to peripheral N-methyl-D-aspartate receptor activation.

Effect of pre-emptive ketamine on sensory changes and postoperative pain after thoracotomy: comparison of epidural and intramuscular routes.

BACKGROUND: In this study we have evaluated the efficacy of ketamine via i.m. and epidural routes for the control of post-thoracotomy pain. METHODS: The study was randomized, double blinded and placebo controlled. With the approval of the Faculty Ethics Committee, 60 patients undergoing elective thoracotomy were randomized into three equal groups. Group IM had i.m. ketamine 1 mg kg(-1) in 2 ml plus epidural normal saline; Group EPI had epidural ketamine 1 mg kg(-1) in 10 ml plus i.m. normal saline; Group C had epidural normal saline 10 ml plus i.m. normal saline 10 ml. Anaesthesia was standardized. Postoperative analgesia was maintained with epidural patient-controlled analgesia using bupivacaine and morphine. Visual analogue scale values and analgesic consumption were evaluated at 2, 4, 6, 8, 10, 12, 24 and 48 h after surgery. The areas of allodynia, pin-prick hyperalgesia and pressure hyperalgesia were measured at 48 h, and days 15 and 30 in all groups. RESULTS: Intraoperative fentanyl requirement was significantly lower in Group EPI than Group C. The morphine and bupivacaine requirements were significantly lower in Group EPI than the other two groups in the postoperative period. There was reduced pin-prick hyperalgesia and touch allodynia in the EPI group. There were no side-effects attributable to ketamine. CONCLUSION: The results of the present study demonstrate that pre-emptive epidural ketamine is effective in reducing intra- and postoperative analgesic requirements, hyperalgesia and touch allodynia.

Sensitivity and distensibility of the rectum and sigmoid colon in patients with irritable bowel syndrome.

BACKGROUND: Hyperalgesia to visceral stimuli is a biological marker of the irritable bowel syndrome (IBS). Abnormal pain processing is probably of most importance, but biomechanical abnormalities of the gut wall may also contribute to the findings. In the current study, we investigated the sensation of the gut to electrical stimuli as well as the distensibility of the rectum and sigmoid colon in IBS patients and a control group. METHODS: Nine patients with IBS and 11 controls entered the study. The pain threshold to electrical stimuli at the rectosigmoid junction was determined with bipolar electrodes integrated on the biopsy forceps for the endoscope. Subsequently, controlled distensions of the sigmoid colon and rectum were performed with a balloon integrated on a probe for impedance planimetry, providing the possibility to measure the cross-sectional area (CSA), wall tension and strain to different pressures together with the sensation ratings. RESULTS: The pain detection thresholds to electrical stimuli at the rectosigmoid junction were 12.5 (range 7-39) mA in controls and 7.5 (range 0.75-12) mA in IBS patients (P = 0.03). The calculated pressures at the pain detection threshold in the sigmoid colon were lower in the IBS patients (31.5 (range 5-58) versus 5 cm (range 5-25) water; P = 0.03), otherwise no differences were seen in sensation rating to the different distension pressures. The CSA was slightly higher in controls to the different pressures, whereas no differences between the groups were seen in strain and tension of the rectum and sigmoid colon. CONCLUSION: The visceral hypersensitivity in IBS seems to be related to alterations in the nervous system rather than biomechanical parameters such as the tension and strain of the gut wall. Treatment of pain in IBS should therefore be based on drugs with documented action on the nociceptive pathways in the central nervous system.

An experimental pain model based on electric stimulations of the colon mucosa.

BACKGROUND: Pain intensity and distribution related to diseases of the gut are important diagnostic indicators in gastroenterology. Experimental pain models provide a unique possibility for standardized activation of the nociceptive system, but only few human models exist. METHODS: An experimental pain model based on electric stimuli in the human colon was developed and applied. Eleven patients who were referred for surveillance colonoscopy due to earlier polyps in the colon were included. None had any abdominal pain complaints. The following areas were stimulated with 'single', 'repeated', or 'continuous' electric current: the cecum, the hepatic and splenic flexures, and the rectosigmoid junction. RESULTS: All subjects felt deep, diffuse pain during the stimulation, with referral to localized somatic structures. The pain detection thresholds after repeated stimuli were similar in the four areas. The threshold for single stimulation was higher than the threshold for repeated stimulation. Most reported pain in the lower and left site of the abdominal wall during stimuli at the splenic flexure and rectosigmoid junction. Stimuli at the right colon, however, resulted mostly in pain at the contralateral site of the abdomen. CONCLUSIONS: The presented model was robust and suitable for eliciting pain in different regions of the large intestine. The importance of temporal summation in visceral pain was shown. Mapping of the referred pain areas mimics clinical observations and has ontogenetic and anatomic consistency. The model may therefore improve the evaluation of pain in patients with diseases of the colon.

Block of pinprick and cold sensation poorly correlate with relief of postoperative pain during epidural analgesia.

OBJECTIVE: To test the following hypotheses: there is a correlation between spread of epidural analgesia as assessed postoperatively by pinprick/cold test and postoperative pain intensity; block of pinprick/cold sensation is associated with absence of postoperative pain. DESIGN: Correlation analysis on prospectively collected data. SETTING: University hospital. PATIENTS: One hundred patients undergoing major surgery. Consecutive sample. INTERVENTIONS: Patients received an epidural infusion of bupivacaine 1 mg/ml, fentanyl 2 microg/ml, and epinephrine 2 microg/ml for at least 48 hours postoperatively. The infusion rate was adjusted according to pain intensity, occurrence of hypotension, or motor block. OUTCOME MEASURES: Assessments were made on three time points: 20-24 hours, 32-36 hours, and 4248 hours after extubation. Assessments included pinprick and cold sensitivity from C2 to S5, pain intensity (visual analogue scale, VAS) at rest, after cough, and after mobilization. Data were analyzed by multiple regression. RESULTS: VAS significantly decreased with increasing spread (number of dermatomes for which hyposensitivity to pinprick or cold was observed). Spread could explain only 2-5% of the variability of VAS. Absence of both pinprick and cold sensation at all dermatomes corresponding to the surgical wound was frequently associated with pain. A high proportion of patients manifesting an upper level of block above T5 had pain after abdominal surgery. CONCLUSIONS: Spread and efficacy of epidural analgesia as assessed by pinprick and cold stimulation correlate poorly with postoperative pain. These methods are of limited value both as clinical indicators of the efficacy of postoperative pain control and for investigating the effect of epidural drugs and techniques.

Hyperexcitability in fibromyalgia.

OBJECTIVE: Spontaneous chronic widespread pain in combination with hyperalgesia to pressure stimuli is the hallmark of fibromyalgia (FM). We tested whether muscular hyperalgesia can exist in a muscle without spontaneous pain, which could indicate a generalized hyperexcitability of the nociceptive system in patients with FM. METHODS: Twelve women with FM and 12 age matched female controls participated in this blind study. Patients had no spontaneous pain in the anterior tibial (AT) muscle. The pressure pain threshold was tested on the AT muscle. The pain threshold to electrical single and repeated stimulations of the skin and of the right AT muscle was assessed. Pain was evoked in the left AT muscle by infusion of sterile hypertonic saline (5.7%, 2.8 ml over 480 s). The saline induced muscle pain intensity and duration were assessed by continuous recordings on an electronic visual analog scale (VAS), and the distribution of pain was assessed on drawings. The sequence of electrical sensibility tests and the infusion of hypertonic saline was randomized. RESULTS: Pressure pain thresholds were lower (p < 0.02) in patients with FM compared to controls. Thresholds for pain evoked by electrical stimulation at the skin were not significantly different in the 2 groups. The pain threshold to repeated intramuscular stimulation was significantly (p = 0.02) lower for the patients with FM compared to the control group, indicating that the temporal nociceptive summation was more pronounced in patients with FM. This is an indication of central sensitization (hyperexcitability). Infusion of hypertonic saline evoked muscle pain with a longer duration (p = 0.01) in patients with FM, and referred pain that spread to a larger area (p = 0.002) than in controls. This is an indication of central hyperexcitability. CONCLUSION: There is a state of central hyperexcitability in the nociceptive system in FM. This hyperexcitability can be revealed by excitation of intramuscular nociceptors in a muscle with no spontaneous pain.

Sensory changes and pain after abdominal hysterectomy: a comparison of anesthetic supplementation with fentanyl versus magnesium or ketamine.

UNLABELLED: Drugs interacting with opioid or N-methyl-D-aspartate (NMDA) receptors may have differing effects on post-surgical sensory changes, such as central inhibition or spinal excitation. We compared the effect of supplementing isoflurane/N2O/O2 anesthesia with an opioid agonist (fentanyl [n = 15]) or two drugs inhibiting the NMDA system differently (magnesium, ketamine [n = 15 in each group]) on sensory changes after abdominal hysterectomy. Electric sensation, pain detection, and pain tolerance thresholds were determined (preoperatively and 1, 4, 24 h, and 5 days postoperatively) in arm, thoracic, incision, and leg dermatomes together with pain scores and cumulative morphine consumption. Thresholds relative to the arm were derived to unmask segmental sensory changes hidden by generalized changes. Absolute thresholds were increased 1-24 h, returning to baseline on Day 5, without overall differences among drugs. Fentanyl thresholds were lower 1 h and higher 5 days postoperatively compared with magnesium and ketamine; thresholds were lower at 24 h for magnesium versus ketamine. Relative thresholds increased compared with baseline only with fentanyl (1-4 h); none decreased. Pain scores and morphine consumption were similar. Thus, all adjuvants suppressed spinal sensitization after surgery. Fentanyl showed the most, and magnesium the least, central sensory inhibition up to 5 days postoperatively, with different patterns of inhibition directly postsurgery versus later. Differences in sensory processing were not reflected in clinical measures. IMPLICATIONS: We studied the effects on postsurgical sensory processing of general anesthesia supplemented by drugs affecting opioid or N-methyl-D-aspartate receptors using sensory thresholds. Generalized central sensory inhibition, differently affected by the drugs, predominated after surgery. All drugs suppressed spinal excitation. Clinical pain measures did not reflect sensory change.

Effects of experimental muscle pain on muscle activity and co-ordination during static and dynamic motor function.

The relation between muscle pain, muscle activity, and muscle co-ordination is still controversial. The present human study investigates the influence of experimental muscle pain on resting, static, and dynamic muscle activity. In the resting and static experiments, the electromyography (EMG) activity and the contraction force of m. tibialis anterior were assessed before and after injection of 0.5 ml hypertonic saline (5%) into the same muscle. In the dynamic experiment, injections of 0.5 ml hypertonic saline (5%) were performed into either m. tibialis anterior (TA) or m. gastrocnemius (GA) and the muscle activity and co-ordination were investigated during gait on a treadmill by EMG recordings from m. TA and m. GA. At rest no evidence of EMG hyperactivity was found during muscle pain. The maximal voluntary contraction (MVC) during muscle pain was significantly lower than the control condition (P < 0.05). During a static contraction at 80% of the pre-pain MVC muscle pain caused a significant reduction in endurance time (P < 0.043). During dynamic contractions, muscle pain resulted in a significant decrease of the EMG activity in the muscle, agonistic to the painful muscle (P < 0.05), and a significant increase of the EMG activity of the muscle, antagonistic to the painful muscle (P < 0.05). Muscle pain seems to cause a general protection of painful muscles during both static and dynamic contractions. The increased EMG activity of the muscle antagonistic to the painful muscle is probably a functional adaptation of muscle co-ordination in order to limit movements. Modulation of muscle activity by muscle pain could be controlled via inhibition of muscles agonistic to the movement and/or excitation of muscles antagonistic to the movement. The present results are in accordance with the pain-adaptation model (Lund, J.P., Stohler, C.S. and Widmer, C.G. In: H. Vaerøy and H. Merskey (Eds.), Progress in Fibromyalgia and Myofascial Pain. Elsevier, Amsterdam, 1993, pp. 311-327.) which predicts increased activity of antagonistic muscle and decreased activity of agonistic muscle during experimental and clinical muscle pain.

Experimental pain in the stomach: a model based on electrical stimulation guided by gastroscopy.

BACKGROUND: Abdominal pain is often variable in intensity and difficult to characterise due to its referred pain pattern. Clinical pain is furthermore confounded by various emotional and cognitive factors. AIMS: To develop and apply an experimental model to induce localised gastric pain. SUBJECTS: Twelve healthy male volunteers. METHODS: Stimulating electrodes were mounted on a biopsy forceps and electric stimuli were delivered during gastroscopy. Single, five repeated, and continuous stimuli were given at four locations in the stomach. Pain detection thresholds and pain intensities were assessed together with localisation of the referred pain area. RESULTS: Pain detection thresholds were higher in the prepyloric region compared with those obtained at the lesser and greater curvature. Increasing stimulus intensity resulted in augmented pain perception and repeated stimuli elicited pain at a lower stimulus intensity than single stimuli. Continuous stimuli evoked constant (33%), increasing (33%), or decreasing (33%) pain. The localisation of referred pain varied considerably in the subjects. CONCLUSIONS: The model seems relevant to study basic pain mechanisms elicited by localised stimuli in the stomach. The experimental data support the premise that a gastric focus should always be suspected in patients referred with different kinds of abdominal pain.