To compare the utility of 0.0625% bupivacaine with fentanyl administered via patient-controlled epidural analgesia (PCEA) to a traditional continuous epidural infusion for pain of labor and delivery.
Forty-one women in established labor were randomized to receive either (a) 0.0625% bupivacaine with 2 micrograms/ml fentanyl via PCEA (demand dose = 3 ml, lockout interval = 6 min, background infusion = 6 ml/h, no 1 or 4 h limits) or (b) 0.125% bupivacaine with 2 micrograms/ml fentanyl via continuous epidural infusion (CEI) at 12 ml/h. Supplemental 0.25% bupivacaine (3 ml every 5 min, p.r.n., x 3) was administered for treatment of breakthrough pain upon patient request. The study protocol was double-blind and placebo-controlled.
Visual analogue pain scores, motor strength, pinprick level of sensory analgesia and bupivacaine use were assessed by an anesthesiologist unaware of the individual patient's randomization to a particular study group.
The cephalad extent of pinprick sensory analgesia was significantly lower during both the first (p < 0.03) and second (p < 0.03) stages of labor in patients receiving PCEA. However, visual analogue pain scores, intensity of motor blockade, and need for physician-administered supplemental bupivacaine were comparable in both groups. Patients receiving PCEA used 40% less bupivacaine per hour while achieving analgesia comparable to patients receiving CEI.
The results of this study show that 0.0625% bupivacaine with 2 micrograms/ml of fentanyl is an effective analgesic combination when used via PCEA.
The aim of the study was to assess whether coadministration of S(+) ketamine or ketorolac would enhance or prolong local analgesic effect of bupivacaine after inguinal hernia repair.
Prospective double-blind randomized study evaluating pain intensity after surgery under general anesthesia.
Outpatient facilities of the University Hospital of Lausanne.
Thirty-six ASA I-II outpatients scheduled for elective day-case inguinal herniorraphy.
Analgesia strategy consisted of a wound infiltration and an inguinal field block either with 30 mL bupivacaine (0.5%) or with the same volume of a mixture of 27 mL bupivacaine (0.5%) + 3 mL S(+) ketamine (75 mg) or a 28 mL bupivacaine (0.5%) + 2 mL ketorolac (60 mg). Postoperative analgesic regimen was standardized.
Pain intensity was assessed with a Visual Analog Scale, a verbal rating score, and by pressure algometry 2, 4, 6, 24, and 48 hours after surgery.
The 3 groups of patients experienced the highest Visual Analog Scale pain score at 24 hours, which was different from those at 6 and 48 hours (P < 0.05). Apart from a significantly lower pain sensation (verbal rating score) in the ketorolac group at 24 and 48 hours and only at 48 hours with ketamine, there were no other differences in pain scores, pain pressure thresholds, or rescue analgesic consumption between groups throughout the 48-hour study period.
The addition of S(+)-ketamine or ketorolac only minimally improves the analgesic effect of bupivacaine. This may be related to the tension-free hernia repair technique associated with low postoperative pain.
Patient-controlled epidural analgesia (PCEA) has been widely used in postoperative pain management. Many factors may correlate with PCEA requirements but no previous study has ever investigated this subject. Therefore, we conducted this study to explore the relationship among patients' characteristics and total PCEA consumption during the 3-day postoperative course.
This prospective study was conducted with surgical patients receiving postoperative PCEA and completing the 3-day course. The PCEA regimen was prepared as 0.0625% bupivacaine with fentanyl (l microg/mL). Patients' characteristics including demographic data and surgical procedures were collected. The total doses were recorded after the course terminated. Stepwise regression analyses were conducted to select significant variables, which could determine total PCEA demand. Subgroup analyses were also performed to investigate whether differences exist among distinct surgical sites.
There were 1753 patients (1094 men and 659 women) included in the analysis. Weight, age, height, body mass index, sex distribution, and total PCEA consumption were significantly different among various surgical sites (all P<0.001). Operational sites, procedures involving malignant disease, weight, and age are the most significant factors in sequence to determine total PCEA requirements. Height and sex have no impact on PCEA demand. The multiple correlation coefficient of our model is 0.688 and the predictive formula of the 3-day postoperative PCEA requirement was 240.1+(130.5xsite)+(66.6xmalignancy)+(1.7xweight)-(0.4xage).
Our study demonstrated the association between patients' characteristics and total PCEA requirements from a large-scaled clinical data. Surgical procedures have more influence on PCEA consumption than demographic variables. Background infusion rate of PCEA could be determined from our predictive model.
The primary objective was to evaluate the clinical safety and effectiveness of the iontophoretic administration of lidocaine HCl 2% and epinephrine 1:100,000 to induce local dermal anesthesia before intravenous (i.v.) cannulation.
Section I: Open, nonblinded. Section II: Randomized, double-blind, placebo-controlled.
Section I: Healthy adult volunteers. Section II: Patients presenting for scheduled outpatient eye surgery.
Section I: Seven healthy adult volunteers. Section II: Forty-four patients requiring i.v. cannulation before scheduled eye surgery.
Section I: Volunteers received iontophoresis of lidocaine HCl 2% with epinephrine 1:100,000 for a total delivery current of 40 mA min. Section II: Patients received iontophoresis for a total delivery current of 40 mA min of lidocaine HCl 2% with epinephrine 1:100,000 (active) or saline (control) immediately before intravenous cannulation with a 20-gauge i.v. catheter.
Section I: Venous blood plasma lidocaine levels, adverse events associated with iontophoresis. Section II: Patient and investigator assessment of analgesia, patient acceptance of iontophoresis, adverse events associated with iontophoresis.
Section I: No detectable levels of lidocaine were identified in any blood plasma sample. Adverse effects were minimal and transitory. Section II: Pain was decreased following lidocaine iontophoresis in comparison with controls, as determined by the patients and investigators. Iontophoresis was well accepted by the patients. Adverse effects were minimal and transitory.
Iontophoresis of lidocaine 2% with 1:100,000 epinephrine for short delivery times does not lead to delivery of clinically important systemic levels of lidocaine in healthy adults. Iontophoresis of lidocaine 2% with 1:100,000 epinephrine provides adequate skin anesthesia for placement of peripheral small-gauge i.v. catheters.
To determine the theoretical repeatability coefficient of a 100 mm VAS in children in different circumstances.
A prospective cohort study was conducted using a convenience sample of patients aged 8 to 17 years presenting to a pediatric emergency department. Patients were asked how they liked a variety of foods (surrogate for stable pain stimulus) on a 100 mm VAS with 4 different sets of questions repeated 3 times: set 1 - questions at 3 minute intervals with no specific instructions other than how to complete the VAS; set 2 - same format as set 1 except for the duration of the interval (1 min); set 3 - same as set 1 except patients were asked to remember their answers; set 4 - same as set 1 except patients were shown their previous answers. For each, the repeatability coefficient of the VAS was determined.
A total of 100 patients aged 12.1±2.4 years were enrolled. The repeatability coefficient for the questions asked at the 3 minute interval was 12 mm while it was 8 mm when asked at the 1 minute interval. When asked to remember their previous answers or to reproduce them, the repeatability coefficients for the questions were 7 mm and 6 mm, respectively.
The conditions of the assessments influence the repeatability coefficient of the VAS. Depending on different circumstances, the repeatability coefficient in children aged 8 to 17 years varies from 6 to 12 mm on a 100 mm VAS.
Electronic pain measures are becoming common tools in the assessment of pediatric pain intensity. The aims of this study were (1) to examine the agreement between the verbal and the electronic versions of the NRS-11 (vNRS-11 and eNRS-11, respectively) when used to assess pain intensity in adolescents and (2) to report participants' preferences for each of the two alternatives.
191 schoolchildren enrolled in grades 7 to 11(Supplemental Digital Content 1-5, http://links.lww.com/CJP/A96, http://links.lww.com/CJP/A97, http://links.lww.com/CJP/A98, http://links.lww.com/CJP/A99, http://links.lww.com/CJP/A100) (mean age=14.61; range=12-18) participated. They were asked to report the highest intensity of the most frequent pain that they had experienced during the last three months using both the vNRS-11 and the eNRS-11. Agreement analyses were done using: (1) the Bland-Altman method, with confidence intervals (CI) of both 95% and 80%, and a maximum limit of agreement of±1; and (2) weighted intra-rater Kappa coefficients between the ratings for each participant on the vNRS-11 and eNRS-11.
The limits of agreement at 95% fell outside the limit established a priori (scores ranged from -1.42 to 1.69), except for participants in grade 11 (Supplemental Digital Content 5, http://links.lww.com/CJP/A100)(-0.80, 0.88). Meanwhile, the limits of agreement at 80% CI fell inside the maximum limit established a priori (scores ranged from -0.88 to 0.94), except for participants in grade 8 (Supplemental Digital Content 2, http://links.lww.com/CJP/A97)(-0.88, 1.16). The Kappa coefficients ranged from 0.786 to 0.912, indicating "almost perfect" agreement. A total of 83% of participants preferred the eNRS-11.
Pain intensity ratings on the vNRS-11 and eNRS-11 seem to be comparable, at least for the 80% CI.
The objective was to assess the analgesic, antihyperesthesic, and anti-allodynic properties of SNX-111 in neuropathic pain.
We describe a patient with refractory, severe deafferentation pain successfully treated with SNX-111 in an open-label, baseline-controlled Phase I/II trial.
The patient was hospitalized for treatment and observation.
The patient was a 43-year-old man with intractable deafferentation pain of 23 years' duration secondary to brachial plexus avulsion.
SNX-111, the first neuron-specific, N-type, voltage-sensitive calcium channel blocker developed for clinical use, was administered by continuous, constant-rate, intrathecal infusion via an indwelling cervical catheter.
The primary outcome measures were the Visual Analog Scales of Pain Intensity (VASPI) and Pain Relief (VASPR).
The patient experienced complete pain relief (VASPI = 0.0 cm and VASPR = 10.0 cm) with elimination of hyperesthesia and allodynia.
SNX-111, administered intrathecally by continuous, constant-rate infusion, produced dose-dependent pain relief in a 43-year-old male patient with a 23-year history of intractable deafferentation and phantom limb pain secondary to brachial plexus avulsion and subsequent amputation. Dizziness, blurred vision, and lateral-gaze nystagmus were dose-dependent side effects that resolved with decreasing dose levels. Complete pain relief was achieved in this patient without side effects after dose adjustment. We conclude that SNX-111 is a potent analgesic, antihyperesthesic, and antiallodynic agent. Controlled studies of SNX-111 in patients with malignant and nonmalignant pain syndromes are warranted and are under way.
From 1984 to 1989, 112 patients with typical drug-refractory trigeminal neuralgia were treated by retrogasserian glycerol injection. The present study assesses results and complications after a mean follow-up period of 3.5 years (range 0.1-5.5 years). One hundred and three of 112 patients (91.9%) showed complete pain relief 1 month postoperatively, and at the end of follow-up 80 patients (71.4%) were still enjoying complete pain relief (recurrence rate 20.5%). Abnormal facial sensations were noted in 49 patients, the most common complication being mild hypoesthesia (32% of patients), while paresthesia occurred in 19% of cases and dysesthesia in 3%. The corneal reflex was absent in 3% of patients and reduced in 5%. None of the patients developed anesthesia dolorosa, permanent masseter weakness, neuroparalytic keratitis, or diplopia.
The present study employed causal modeling to examine the impact of somatic and cognitive symptoms of depression on the functioning of patients with chronic pain.
Path analyses were conducted to determine whether pain level is directly related to the psychosocial and physical dimensions of functional status or whether this relationship is mediated by depression.
Subjects were recruited from a facial pain clinic at the University of Florida, an outpatient clinic associated with a tertiary-care health center.
Subjects were 70 patients with chronic pain, 53 of whom had primary facial pain.
All subjects completed a packet of self-report questionnaires, including the Beck Depression Inventory, McGill Pain Questionnaire, and Sickness Impact Profile.
Results of path analyses indicated that both somatic and cognitive symptoms of depression significantly correlate with psychosocial functioning even after controlling for the effects of pain level, trait anxiety, and trait anger. Somatic symptoms of depression were significantly correlated with physical functioning after pain level, anxiety and anger were controlled.
This study indicates that depression is directly related to both the physical and the psychosocial functioning of facial pain patients, while self-reported level of pain is not. A better understanding of the impact of depression on chronic pain and the relationship of these two disorders could lead to improved assessment and treatment of chronic pain disorders.
The synthetic opioid methadone has generated much interest in recent years among clinicians involved in the management of intractable chronic cancer pain. Its use as an analgesic is starting to extend to the treatment of noncancer pain, particularly neuropathic pain. Unfortunately, the evidence for its use in the management of neuropathic pain is limited to a few case studies. We examined retrospectively during a 12-month study period the clinical response of all 13 patients at our pain clinic who were prescribed methadone in an attempt to control neuropathic pain resistant to conventional analgesics. A questionnaire was also administered to the 9 patients who continued to take methadone at 12 months posttreatment. A total of 4 patients (31%) discontinued it by the end of the 12-month study period. Patients discontinued methadone due to the absence of pain relief and due to various intractable, undesirable side effects. Somnolence was the most common adverse effect reported, followed by nausea, constipation, and vomiting. All patients took coanalgesics (eg, amitriptyline, gabapentin) or other analgesics (eg, morphine, nonsteroidal anti-inflammatory drugs) during methadone treatment to control pain. The 9 patients who continued to take methadone at 12 months reported experiencing on average 43% pain relief (range 0-80%), 47% improvement in quality of life (range 0-100%), and 30% improvement in quality of sleep (range 0-60%). Methadone was effective at relieving pain and ameliorating quality of life and sleep in 62% of patients. These findings suggest that methadone can offer an acceptable success rate for the treatment of neuropathic pain. Prospective randomized, placebo-controlled studies are now needed to examine more rigorously the benefits of methadone for this type of pain.
To review the (1) reliability, validation, feasibility, and clinical utility and (2) the use of the Premature Infant Pain Profile (PIPP) from 1996 to 2009 to determine the effectiveness of pain management strategies.
Data sources included MEDLINE, CINAHL, EMBASE, PsycINFO, and the Web of Science. Published studies evaluating the measurement properties of the PIPP and intervention studies using the PIPP as an outcome measure of acute pain were included. One reviewer screened studies for relevance and inclusion. Four reviewers rated intervention studies for methodological quality and extracted data for the evidence tables.
Of the 62 studies included, 14 focused on the measurement properties of the PIPP. Reliability of the PIPP was supported in 5 studies and construct validation was supported in 13 studies. The feasibility of the PIPP was addressed in 4 studies, whereas clinical utility was discussed in 2 studies. Twenty-seven of the 48 studies that were considered to have high methodological quality used the PIPP as the major outcome to evaluate the effectiveness of pain management interventions in infants.
The PIPP continues to be a reliable and valid measure of acute pain in infants with numerous positive validation studies. There is substantial support for the use of the PIPP as an effective outcome measure in pain intervention studies in infants. Further research with health professionals is required to better support the feasibility and clinical utility of this measure.
One hundred fifty randomly selected hospitalized children between the ages of 4-14 were interviewed to assess their pain experience in the hospital. Follow-up information was obtained through parent interviews 3 weeks, 3 months, and 6 months later. On enrollment, more than 87% of children reported having had pain within 24 h and, of those, 19% reported their usual pain intensity as in the severe range. Thirty-eight percent of children had received analgesic medication during the preceding 24 h. Children who had undergone surgery were three to four times more likely to have received narcotic analgesic than nonsurgical patients, although similar proportions in both groups reported moderate to severe pain intensity. In spite of these reports of significant pain by a substantial number of children during hospitalization, at the 3-week follow-up check, by parent report, 68% were pain free. The parents of those with pain were contacted at 3 and 6 months postenrollment, and 96% of children were no longer experiencing pain. Five children reported pain at all contact points; three of these were suffering chronic diseases and the other two had suffered major trauma from motor-vehicle accidents.
The objective of this article was to review the positive scientific data on antidepressants and opioids, which are largely confined to randomized controlled trials in two neuropathic pain conditions that have proved to be good models for clinical investigation. These two disorders are postherpetic neuralgia and painful diabetic neuropathy.
This is a review of the literature using MEDLINE, CINAHL, and the Cochrane Database.
There is extensive literature supporting the use of the older antidepressants such as amitriptyline in neuropathic pain. Newer randomized controlled trials support the use of opioids.
First-line therapy for neuropathic pain may be either an older generation antidepressant such as amitriptyline or nortriptyline or the anticonvulsant gabapentin. For refractory cases, chronic opioid therapy may be the only avenue of relief, and evidence is accumulating that this approach is safe if proper guidelines are observed.
The aims of this multicenter, randomized, placebo-controlled, double-blind trial were to confirm the efficacy of lacosamide at a daily dose of 400 mg/d and to explore the efficacy, safety, and tolerability of lacosamide 200 mg/d and 600 mg/d in the treatment of painful diabetic neuropathy.
The trial consisted of a 2-week run-in period, a 6-week titration phase, and a 12-week maintenance phase, during which patients received placebo or fixed doses of lacosamide 200, 400, or 600 mg/d. No back titration was allowed during the trial. The primary efficacy criterion was the change in Likert pain score from baseline to the average over the last 4 weeks of the maintenance phase in the intent-to-treat population.
The lacosamide 400 mg/d group demonstrated statistically significant improvement in Likert pain score over placebo for the primary efficacy measure. At the end of treatment, 58% of patients in the lacosamide 400 mg/d treatment group achieved at least a 2-point or 30% reduction in Likert pain score, compared with 46% of placebo-treated patients. The lacosamide 200 mg/d group separated from placebo, but failed to show statistical significance for any of the primary or secondary outcome measures. The lacosamide 600 mg/d group was significantly more efficacious than placebo in the observed cases but not in the intent-to-treat population. This was probably secondary to a relatively high-premature withdrawal rate due to adverse events that occurred during the titration phase in that group. Overall lacosamide at daily doses of 200 to 400 mg was well tolerated, with 8% of patients discontinuing due to an adverse event from the 200 mg/d group and 23% from the 400 mg/d group compared with 9% in the placebo group. Discontinuations due to adverse events were highest in the 600 mg/d group (40%). The most common adverse events consisted of dizziness, nausea, tremor, headache, and fatigue. Somnolence, cognitive and behavioral side effects, weight change, and edema were notably low.
Safety and efficacy analyses indicated that lacosamide 400 mg/d provided an optimal balance between efficacy and side effects in patients with painful diabetic neuropathy.
The current study assessed stability of pain coping strategies over an 18-month period in adults, adolescents, and young children with sickle cell disease.
Eighteen-month longitudinal study. Assessments of coping strategies were done at baseline, 9 months, and 18 months.
A total of 141 patients with sickle cell disease (SCD) presenting to adult and pediatric sickle cell clinics for regularly scheduled check-ups.
Coping Strategy Questionnaire subscales (Coping Attempts, Negative Thinking, and Illness-Focused Strategies).
pearson Product-Moment correlation coefficients comparing baseline and 18-month follow-up coping data were highly significant for Coping Attempts and Negative Thinking/Illness Focused Strategies for adults. For young children, the 18-month follow-up scores on Negative Thinking were significantly correlated with baseline scores, however, no other 18-month correlations were significant. The results from the adolescent subset of subjects indicated no significant correlations on any of the coping strategies from baseline to 18-month-follow-up. Stability was also assessed using intraclass correlations, which incorporates more than two test-retest values on the same subjects. These analyses confirmed that coping strategies in adults were highly stable, whereas for children and adolescents, there was instability ANOVAs indicated that adolescents scored significantly higher than young children on Negative Thinking and Illness-Focused Strategies at baseline and follow-up.
As compared with the highly stable coping evidenced in adults with SCD, coping in children and adolescents with SCD is more variable. Thus, interventions should target children early before maladaptive coping patterns become entrenched.
Thirty-six subjects participated in an 18-month follow-up of a secondary prevention program for back pain of recent onset. The follow-up assessment included most of the same instruments used in the original study. In addition, interviews were conducted to ascertain help and hindrance factors for maintaining improvements during the follow-up period. Results showed that subjects had significantly less pain, used fewer medications, and were more active at 18-month follow-up than at baseline. All subjects had returned to work, and one third had no pain-related work absences during the follow-up. A cost-benefit analysis indicated substantial economic savings when follow-up sick-listing data were compared with estimates based on an increasing trend for pain-related absenteeism found during the baseline period. Hindrance factors reported by subjects were related to personal time-management and workplace factors, especially psychosocial aspects of the work environment. It was concluded that the secondary prevention program was effective and that future maintenance programs should focus more on personal time-management and workplace factors.
The aim of this study was to evaluate the efficacy of a systemic application of rhenium-186 hydroxyethylidenediphosphonate (Re HEDP) for pain treatment in patients with hemophilic arthropathies.
Twelve patients with hemophilic arthropathy with at least 3 involved joints with persistent pain were included in this prospective study. A single dose of 15 mCi (555 MBq) Re HEDP was administered intravenously. Before and 12 weeks after treatment, pain assessment was performed using the visual analog scale (VAS). The pain status assessment included the general status, pain of all joints affected, and pain of the 3 mostly involved joints. Furthermore, quality of life was assessed.
With regard to the 3 most involved joints, an improvement of the pain symptoms in 25 of 36 (69.4%) joints was observed. With regard to all involved joints a median of 3 joints per patient improved after Re HEDP therapy. General pain status after treatment was 2.0 VAS points lower as compared with pretreatment. The total number of involved joints remained unchanged in 7 patients, increased in 1 patient, and decreased in the remaining 4 patients.
The results of this study show an improvement of the pain symptoms of the involved joints 12 weeks after therapy with Re HEDP in patients with hemophilic arthropathy. The only moderate success regarding a reduction of the total number of involved joints is by the fact that despite this improvement most affected joints remained still painful on a lower level after the therapy or due to newly affected joints not painful before initiation of the radionuclide therapy.
The objective was to assess the reported use in recent publications of the diagnostic criteria for complex regional pain syndrome type I (CRPS I) proposed by the International Association for the Study of Pain (IASP) in 1994.
A literature search of MEDLINE (January 1996 to July 2000) was performed with use of the medical subject heading "reflex sympathetic dystrophy" and the free texts words "complex," "regional," "pain," and "syndrome." Publications in English, German, and Dutch were analyzed. From the search, 65 original publications were selected. Another 27 publications (referenced publications) that were referenced in the 65 original publications for the description of diagnostic criteria for CRPS I also were included. A standard form was used to assess a total of 92 publications. A sensitivity analysis was performed by means of analyzing three scenarios in which the diagnostic criteria were used as proposed and two combinations of less stringent criteria.
Use of the diagnostic criterion pain was reported in 35 (38%) of the analyzed publications. None of the original publications satisfied the proposed IASP diagnostic criteria. Four (15%) of the referenced publications satisfied the proposed IASP diagnostic criteria. Ten (15%) of the original publications referred correctly to the referenced publications. With the less strict criteria used in scenarios 2 and 3, 2 (3%) and 3 (5%), respectively, of the original publications fulfilled these criteria.
If the diagnostic criteria for CRPS I are not used uniformly, the populations in clinical studies may not be uniform either. Whether different authors are describing the same syndrome and whether their findings can be compared is open to question. On the basis of the results of this study, it is concluded that the IASP criteria for CRPS I are poorly used in clinical studies.
There has been a longstanding recognition that adult patients with chronic pain are not a homogenous population and that there are subgroups of patients who report high levels of distress and interpersonal difficulties as well as subgroups of patients who report little distress and high functioning. The purpose of the present study was to attempt to identify similar subgroups in a pediatric chronic pain population.
The sample consisted of 117 children with chronic pain and their parents who were assessed in a multidisciplinary pain clinic during 2001. Participants completed a set of psychologic self-report questionnaires, as well as demographic and pain characteristic information. A cluster analysis was conducted to identify 3 distinct subgroups of patients to replicate similar studies of adult chronic pain sufferers.
Overall, mean scores were within population norms on measures of distress and family functioning, with somatic symptoms at a level of clinical significance. The cluster analysis identified the 3 subgroups that were strikingly similar to those identified in adult chronic pain populations: one with high levels of distress and disability, another with relatively low scores on distress and disability, and a third group that scored in between the other 2 on these measures but with marked low family cohesion.
The similarity of these subgroups to the adult chronic pain population subgroups as well as implications for future studies are discussed.
Previous studies have suggested that many inflammatory cytokines, including interleukin (IL)-1α, may be associated with lumbar radicular pain after disc herniation. In the present study, we examined how variability of the IL-1α gene affects pain intensity and the pressure pain threshold in patients with symptomatic disc herniation.
A total of 121 patients with lumbar radicular pain due to disc herniation were recruited from Oslo University Hospital, Norway, and followed up at 6 weeks and 12 months. The primary outcome measures were pain intensity scores for the lower back and legs using a visual analog pain scale (VAS) and pressure pain threshold (PPT) for the gluteal muscles. Genotyping was carried out using a predesigned TaqMan assay for IL-1α rs1,800,587. The effect of the IL-1α genotype on the VAS and PPT was analyzed by repeated measure analyses of variance.
The IL-1α gene C>T polymorphism rs1,800,587 affected VAS and PPT scores in patients with symptomatic disc herniation. Patients with the CT/TT genotype reported a higher VAS leg pain intensity (P=0.002) and also a lower PPT in the gluteal muscles (left P=0.016; right P=0.016) compared to patients with the CC genotype during 1 year of follow-up.
The present data show that the IL-1α CT/TT genotype rs1,800,587 may be associated with increased pain intensity, and corresponding reduced pressure pain threshold during the first year after disc herniation.
This study estimates the costs to society of prescription opioid analgesic (RxO) abuse in the United States.
Costs associated with RxO abuse were grouped into healthcare, criminal justice, and workplace categories. Costs were estimated by either (1) a quantity method that multiplies the number of RxO abusers derived from various national surveys by the estimated per abuser cost, or (2) an apportionment method that starts with overall (ie, prescription and nonprescription) drug abuse costs for a cost component (eg, police protection) and apportions the share of costs based on the prevalence of RxO abuse relative to overall drug abuse. Medical costs in excess of those for otherwise similar nonabusers were based on an analysis of a large administrative claims database for an employed population using multivariate regression methods.
A lower bound estimate of the costs of RxO abuse in the United States was 8.6 billion dollars in 2001 (or 9.5 billion dollars in 2005 dollars). Of this amount, 2.6 billion dollarswere healthcare costs, 1.4 billion dollars were criminal justice costs, and 4.6 billion dollars were workplace costs.
The costs of RxO abuse represent a substantial economic burden. Rising trends of RxO abuse suggest an escalating economic and public health burden in coming years in the United States, and potentially, elsewhere.
Opioid-related mortality has increased in the United States in the past decade. The purpose of this study was to examine trends and regional variation in opioid prescribing and overdose rates in a national health system, the Veterans Health Administration (VHA).
Annual cohorts of VHA patients were identified based on medical records and overdose mortality was determined from National Death Index records. State-level prescribing and overdose rates were mapped to provide information on regional variability.
There were significant increases between 2001 and 2009 in the rate of overdoses associated with non-synthetic opioids (β=0.53, 95% CI: 0.35, 0.70) and methadone (β=0.63, 95% CI: 0.37, 0.90) but not synthetic/semi-synthetic opioids. State-level overdose rates had a moderate correlation with the average proportion of patients in that state receiving opioids (r=0.29).
The present study demonstrates that the increases in prescription opioid overdoses observed in the general population are also found in the patient population of a national health system and provides further evidence of the population-level association between trends in opioid prescribing and opioid overdose deaths. There is substantial regional variation in both opioid prescribing and opioid-related overdose rates, and these data can inform region-specific overdose prevention strategies and opioid policy.
Two acromegalic patients with severe headache, persisting after pituitary adenomectomy followed by radiotherapy in one, were treated with the somatostatin analogue SMS 201-995. Both had been resistant to conventional headache therapy and experienced dramatic and rapid relief after the first injection of the analogue. This result persisted with long-term treatment of the drug. Although the mechanism of action of SMS 201-995 in pain remains unclear, the rapid and efficacious analgesic effect of this compound may be one more indication for its use in pituitary tumors associated with cephalalgias.
While microRNAs (miRNAs) have been shown to play a role in numerous biological processes, their function in neuropathic pain is not clear. The rat bilateral sciatic nerve chronic constriction injury (bCCI) is an established model of neuropathic pain, so we examined miRNA expression and function in the spinal dorsal horn in bCCI rats.
Microarray and real-time PCR were used to examine the expression of microRNA in nerve system of bCCI rats, and the targets of miRNA were predicted by bioinformatic approaches. The function of specific miRNA was estimated through the methods of gene engineering.
This study revealed substantially (∼10-fold) decreased miR-203 expression in the spinal dorsal horns, but not the dorsal root ganglions, hippocampus, or anterior cingulate cortexes of bCCI rats. Rap1a protein expression was up regulated in bCCI rat spinal dorsal horns. We further verified that miR-203 directly targeted the 3'-untranslated region of the rap1a gene thereby decreasing rap1a protein expression in neuron-like cells.
Rap1a has diverse neuronal functions and their perturbation is responsible for several mental disorders. For example Rap1a/MEK/ERK is involved in peripheral sensitization. These data suggest a potential role for miR-203 in regulating neuropathic pain development, and Rap1a is a validated target gene in vitro. Results from our study and others indicate the possibility that Rap1a may be involved in pain. We hope that these results can provide support for future research into miR-203 in gene therapy for neuropathic pain.
Investigations of the association between chronic pain conditions and suicidal ideation (SI) and suicide attempts (SA) have rarely taken the effect of mental disorders into account and have been limited by nonrepresentative samples. The present study used a large population-based sample to investigate the association between chronic pain conditions and SI and SA.
Data were from the Canadian Community Health Survey Cycle 1.2 public use file conducted by Statistics Canada from 2001 to 2002 (N=36,984; response rate 77%). Respondents were asked if they had been diagnosed with the following painful conditions: migraine, back problems, arthritis, and fibromyalgia. Respondents were assessed for past 12-month SI and SA. The Composite International Diagnostic Interview was used to assess Diagnostic and Statistical Manual of Mental Disorders-IV.
After adjusting for sociodemographics, Axis I mental disorders and comorbidity (3 or more mental disorders), the presence of 1 or more chronic pain conditions was associated with both SI and SA. Among respondents with a mental disorder, comorbidity with 1 or more chronic pain conditions was also associated with SI and SA. In models adjusting for other painful conditions, migraine had the strongest link with SI and SA.
This is the first study to demonstrate the association between several chronic pain conditions and SI and SA while adjusting for mental disorders in a nationally representative sample. Moreover, this study demonstrates that among individuals with a mental disorder, having a chronic pain condition significantly increased the association with SI and SA.
Trigeminal neuralgia may be treated in several ways. In the present study, the efficacy of a selective percutaneous radiofrequency (RF) neurolysis in the gasserian ganglion was evaluated in 240 patients. The recurrence rate after a single treatment was 28.3% within 2 years. After multiple treatments (n = 68), the recurrence rate had decreased to 8.3% (n = 20). Thus, the overall success rate at the end of the follow-up period was 91.7%. The mean follow-up period was 50 months (range 12-96 months). Except for corneal anesthesia in 3.7% of the patients, no serious complications occurred.
Persistent pain after breast cancer surgery is an underrecognized problem. Self-reporting is uncommon in the Chinese community.
In this study, 200 women completed questionnaires assessing prevalence and associated factors of persistent pain after breast cancer surgery.
28.5% women reported persistent pain after surgery, 50.5% women reported sensory disturbance, and 4.2% reported phantom breast pain. The report of higher pain score was associated with a higher pain disability index score.
The findings suggest that persistent pain after breast cancer surgery is a significant problem among Chinese women in Hong Kong and affects their quality of life.
In a multicenter study, 28 patients with cancer pain and insufficient pain relief with analgesic treatment according to step II of the guidelines of the World Health Organization (WHO) were switched to oral slow-release morphine.
Patients received intravenous morphine through a patient-controlled pump (PCA) for the first 24 hours (bolus = 1 mg, lockout interval = 5 minutes, maximum dose = 12 mg/hour). From day 2 patients were treated with oral slow-release morphine. Daily doses were calculated from the requirements of the day before. Breakthrough pain was treated with PCA until stable doses were reached (<2 boluses/day) and then with oral immediate-release morphine solution. Pain intensity was reported in a diary four times a day, in addition to mood, activity, and quality of sleep once daily.
Mean duration until adequate pain relief reported (<30 on a 101-step numerical scale; NRS) was 5 hours (range = 80-620 minutes). Mean pain intensity was reduced from 67 NRS to 22 NRS. Mean doses of oral morphine were 133 mg/day initially and then 154 mg/day on day 14. Serious adverse events such as respiratory depression were not observed. Two patients terminated the study due to progressive symptoms of gastrointestinal obstruction. Seventy-five percent of the patients evaluated the effectiveness of the analgesic regime as good.
Dose finding with intravenous PCA may be appropriate for a small minority of patients with severe pain. Higher treatment costs and the risk of complications are drawbacks of this method compared with conventional oral titration.
Preterm infants undergo frequent painful procedures in the neonatal intensive care unit. Electroencephalography (EEG) changes in reaction to invasive procedures have been reported in preterm and full-term neonates. Frontal EEG asymmetry as an index of emotion during tactile stimulation shows inconsistent findings in full-term infants, and has not been examined in the context of pain in preterm infants. Our aim was to examine whether heel lance for blood collection induces changes in right-left frontal asymmetry, suggesting negative emotional response, in preterm neonates at different gestational age (GA) at birth and different duration of stay in the neonatal intensive care unit.
Materials and methods:
Three groups of preterm infants were compared: set 1: group 1 (n=24), born and tested at 28 weeks GA; group 2 (n=22), born at 28 weeks GA and tested at 33 weeks; set 2: group 3 (n=25), born and tested at 33 weeks GA. EEG power was calculated for 30-second artifact-free periods, in standard frequency bandwidths, in 3 phases (baseline, up to 5 min after heel lance, 10 min after heel lance).
No significant differences were found in right-left frontal asymmetry, or in ipsilateral or contralateral somatosensory response, across phases. In contrast, the Behavioral Indicators of Infant Pain scores changed across phase (P<0.0001). Infants in group 1 showed lower Behavioral Indicators of Infant Pain scores (P=0.039).
There are technical challenges in recording EEG during procedures, as pain induces motor movements. More research is needed to determine the most sensitive approach to measure EEG signals within the context of pain in infancy.
Previous studies indicate that genetic variants in genes encoding proteins like matrix metalloproteinase (MMP) enzymes may affect degeneration of the intervertebral disk. One such genetic variant is a single nucleotide polymorphism insertion in the promoter region of the MMP1 gene, that is, the MMP1 rs1799750 2G allele, which increases the MMP1 expression in vitro. In this study, we examined whether the MMP1 rs1799750 2G allele might be associated with disk degeneration and clinical outcome after lumbar disk herniation.
Materials and methods:
A total of 260 patients with lumbar disk herniation and sciatic pain were included in this study and genotyped for the MMP1 rs1799750 2G allele.
The present data showed no differences in the frequency of the MMP1 2G allele in patients recently diagnosed with disk herniation compared with pain-free controls. Moreover, in the patients, the MMP1 2G allele was not directly related to the disk degeneration. However, our data demonstrated that the MMP1 2G allele was associated with both pain and disability, that is, increased visual analog scale score, McGill Pain Questionnaire score, and Oswestry Disability Index score. Clearly, the patients homozygous for the 2G allele had more pain and reduced function compared with those carrying the 1G allele.
Our findings suggest that the MMP1 rs1799750 2G/2G genotype may contribute to low back pain, sciatica, and disability after lumbar disk herniation.
In the pituitary of lower species, pro-opiomelanocortin is expressed in corticotroph cells of the anterior and in melanotroph cells of the neurointermediate lobe; enzymatic processing in the corticotrophs results in the release of adrenocorticotropic hormone, beta-lipotropin, or beta-endorphin. In the melanotrophs, these fragments are further modified, eg, by N-terminal acetylation. In the human pituitary, these enzyme systems are located within the same cells in the anterior lobe. We studied the reactions of the pro-opiomelanocortin system under preoperative conditions as well as under postoperative pain.
In 17 patients undergoing hip or knee arthroplasty, we determined plasma concentrations of N-acetyl-beta-endorphin immunoreactive material, authentic beta-endorphin [beta-endorphin(1-31)], adrenocorticotropic hormone, beta-lipotropin immunoreactive material, and cortisol, as well as pain severity rated by the patients using a visual analogue scale before surgery, after surgery but still under spinal anesthesia, under postoperative pain, and 1 day after surgery.
Only low levels of N-acetyl-beta-endorphin immunoreactive material were measured in 16 out of 17 patients. High concentrations (1st quartile/median/3rd quartile; pmol/L) of adrenocorticotropic hormone (22.5/55.8/124) and beta-lipotropin immunoreactive material (6.6/34.6/142) were observed under postoperative pain, accompanied by a small increase of beta-endorphin(1-31) concentrations (0.0/6.1/10.9). Preoperatively small but significantly elevated levels of corticotroph-type and melanotroph-type pro-opiomelanocortin derivatives were observed; in contrast, spinal anesthesia suppressed all pro-opiomelanocortin fragment release. Postoperative pain severity correlated with postoperative adrenocorticotropic hormone, beta-lipotropin immunoreactive material, and beta-endorphin(1-31) concentrations.
We conclude that the melanotroph-type pro-opiomelanocortin system is not activated under postoperative pain; the increase of corticotroph-type pro-opiomelanocortin fragment levels is different in quantity and proportion under preoperative conditions or postoperative pain, respectively.
The purpose of this study was to examine the influence of prone and supine position in preterm infants during acute pain of blood collection.
Level III Neonatal Intensive Care Unit (NICU).
Thirty-eight preterm infants (birthweight 1339 [590-2525] g, GA 29 [25- 32] wks) were in 2 groups depending on their position in the isolette prior to and during heel lance at 32 weeks post-conceptional age. The study design was a comparison between groups (Prone, Supine) during 2 events (Baseline, Heel lance).
Pain measures were multidimensional, including behavioral (sleep-wake state and facial activity) and physiological (heart rate) responses measured continuously prior to (Baseline) and during blood collection (Lance).
Both groups of infants displayed statistically significant shifts in sleep-wake state to greater arousal, and increased facial activity and heart rate, from Baseline to Lance. Prone position was associated with significantly more deep sleep during Baseline, compared with Supine position, but there were no differences in sleep-wake state during Lance. Minor increased facial activity was shown in some time segments of Baseline for infants in Supine compared with Prone, but did not differ overall between positions. Prone and Supine position did not affect heart rate significantly during Baseline or Lance events.
Prone position promotes deep sleep in preterm neonates at 32 weeks post-conceptional age when they are undisturbed. However, placement in prone position is not a sufficient environmental comfort intervention for painful invasive procedures such as heel lance for blood sampling in the NICU. Neonates require other environmental supports to promote coping with this stressful event.
To compare biobehavioral pain responses of preterm infants born at differing gestational ages (GAs) when pain was preceded by a rest period or by a series of routine nursing interventions.
In a randomized, within subjects, cross-over design, facial (Neonatal Facial Coding System), sleep/wake state and heart rate (HR) responses of 43 preterm infants [mean birth weight: 1303 g (range 590 g to 2345 g); mean GA at birth: 30 weeks (range 25 to 32)] were examined across 3 phases of blood collection (Baseline, Lance, and Recovery) under 2 conditions: pain after a 30-minute rest period versus pain after a series of routine nursing interventions (clustered care). Infant behavioral responses were coded from continuous bedside videotapes. HR was analyzed using custom physiologic signal processing software.
Infants born at earlier GA (<30 wk) had equally intense facial responses during the Lance phase regardless of condition. However, later born infants (> or =30 wk GA) showed heightened facial responses indicative of sensitized responses during blood collection when it was preceded by clustered care (P=0.05). Moreover, later born infants had significantly lower facial (P=0.05) and HR (P=0.04) reactivity during Recovery when blood collection followed clustered care.
Earlier born preterm infants showed heightened states of arousal and poor ability to modulate HR during Recovery when an invasive procedure was preceded by routine tactile nursing procedures. Alternatively, later born infants exhibited sensitized responses when clustered care preceded blood collection. Our findings support the importance of cue based individualized approaches to care.
The present retrospective case review study sought to analyze the cost-utility, expressed in cost/quality-adjusted life years (QALY), of current chronic spinal pain treatments. In addition, it expands upon previously published data evaluating the efficacy of interdisciplinary pain management in relation to medication management.
A recently developed algorithm was used to calculate QALYs using SF-36, v. 1 responses for 121 patients receiving treatment for chronic spinal pain at a pain rehabilitation center. Treatment groups evaluated were: (1) interdisciplinary program completers who received medication management and supplementary anesthetic procedures; (2) interdisciplinary program completers receiving medication management but not anesthetic procedures; (3) patients receiving medication management alone; and (4) patients receiving medication management with supplemental anesthetic procedures. Assessments were conducted at pretreatment and 6 months after the initiation of treatment.
One-way analyses of covariance indicated that patients who participated in an interdisciplinary pain management program, which included medication management, psychotherapy, group education, and physical therapy, reported significantly less impairment in daily activities of living, less subjective experience of pain, and a higher quality of life and more preferred health state at the completion of their treatment phase, relative to patients receiving medication with or without anesthetic procedures. In addition, improvements in all outcome measures between pretreatment and posttreatment were significantly greater for those patients completing the interdisciplinary component of treatment. Cost-utility analyses revealed that the interdisciplinary treatment alone group was cost-saving, relative to the medication and procedures alternative, suggesting the former modality was both less costly and more effective than the latter.
Average cost-utility ratios for both interdisciplinary treatment groups, ranging from 57,627 dollars /QALY to 75,885 dollars /QALY, were within established cost-effective parameters (20,000 dollars to 100,000 dollars /QALY, generally considered a good value), whereas cost-utility ratios for the standard care treatment groups were not interpretable because of a decrease in QALYs from pretreatment to posttreatment.
The Short Form-36 (SF-36) and Migraine Disability Assessment (MIDAS) questionnaires are two of the most commonly used tools to measure outcomes in people suffering from headaches. Nevertheless, little is known about their interrelationship in patients with headache.
The aim of this study was to investigate the interrelationship between SF-36 and MIDAS questionnaires in patients with migraine.
We enrolled 231 patients with migraine (male/female: 43/188, mean age 35.3+/-8.1) who visited our headache clinic. They completed the SF-36, MIDAS, and a headache intake form.
The correlation coefficients between the MIDAS score and 8 domains of the SF-36 ranged from -0.30 for the mental health domain to -0.53 for the social functioning domain (P<0.01). Canonical correlation analysis showed that the overall overlap between the 2 instruments was moderately strong (canonical correlation coefficients r=0.707 and 0.572). The overall measured redundancies for MIDAS and SF-36 scales in this study were 35.4% and 11.5%, respectively. The stepwise linear regression model showed that the social functioning domain alone explained 27.9% of variance in the MIDAS scores. Bodily pain, physical functioning, and general health domains added an additional 11.4% of the explained variance in the regression model.
Despite the fact that these two measures were considerably correlated, the MIDAS and SF-36 were found to measure different aspects of the impact of headache for the sample investigated. The MIDAS questionnaire does not cover the emotional domain; therefore, an accompanying psychological questionnaire might help assess the outcome for headache studies.
We describe the 3-dimensional (3D) image-guided placement technique for a lumbar intrathecal catheter through a dorsal fusion mass. This is the first time this technique has been reported. A patient with 6 prior spine surgeries and chronic pain syndrome presented with a challenging large dorsal fusion mass. The use of 3D cone beam computed tomography-based image guidance proved advantageous for the placement of an intrathecal drug delivery system (IDDS).
Under general anesthesia, image guidance was accomplished with the Medtronic Stealth S7 image guidance system, used in conjunction with the O-ARM (Medtronic Inc.). Using an image-guided probe over the skin surface, we navigated the dorsal fusion mass to identify a thin area at the L4-L5 level. A small incision was made and the image-guided probe was used to target the selected thin area and drill an adequate opening in the fusion mass. We inserted a Tuohy needle through the bony defect for passage of the intrathecal catheter. We confirmed adequate catheter placement using free flowing cerebrospinal fluid and fluoroscopy. The remainder of the IDDS implant proceeded per routine.
The patient tolerated the procedure well and had no complications. The morphine IDDS improved his overall pain and function with minimal side effects.
This is the first case report using 3D cone beam computed tomography-based image guidance for the placement of an intrathecal catheter through a bony fusion mass. This technique appears to be a viable option for IDDS implantation in patients with difficult anatomy.
Analyses of integrated data from 4 controlled postherpetic neuralgia studies evaluated the effect of NGX-4010, a capsaicin 8% patch, administered alone or together with systemic neuropathic pain medications.
Patients recorded their “average pain for the past 24 hours” daily for 12 weeks using an 11-point Numeric Pain Rating Scale (NPRS). Efficacy assessment included the percentage NPRS score reduction from baseline during weeks 2 to 8 and 2 to 12, the proportion of patients responding during weeks 2 to 8 and 2 to 12 and the Patient Global Impression of Change (PGIC) at weeks 8 and 12.
During the studies, 302 NGX-4010 and 250 control (capsaicin, 0.04% wt/wt) patients were using at least 1 systemic neuropathic pain medication; 295 NGX-4010 and 280 control patients were not. During weeks 2 to 8, NGX-4010 patients reported greater reductions in NPRS scores compared with control both in patients using systemic neuropathic pain medications (26.1% vs. 18.1%, P=0.0011) and in patients not using these medications (36.5% vs. 26.2%, P=0.0002). Patients not using systemic neuropathic pain medications reported a greater reduction in pain compared with patients using these medications in both, NGX-4010 and control groups, resulting in comparable treatment differences between NGX-4010 and control regardless of systemic neuropathic pain medication use. Similar results were seen during weeks 2 to 12, for the responder and PGIC analyses. Transient, capsaicin-related application site reactions were the most common adverse events and not affected by systemic neuropathic pain medication use.
A single 60-minute NGX-4010 treatment reduces PHN for up to 12 weeks regardless of concomitant systemic neuropathic pain medication use.
To evaluate the efficacy, safety, and tolerability of repeated NGX-4010 treatments in the open-label extension phase of a 52-week study in patients with neuropathic pain due to HIV-associated distal sensory polyneuropathy (HIV-DSP).
Patients completing the 12-week, randomized, double-blind phase of the study could enter a 40-week, open-label phase, and receive up to 3, 60-minute NGX-4010 treatments. Patients recorded their "average pain for the past 24 hours" daily using the Numeric Pain Rating Scale (NPRS). Efficacy assessment included the percentage NPRS score reduction from baseline to weeks 2 to 12 after the final treatment, and Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) questionnaires at study termination.
Of 307 patients randomized, 272 entered the open-label phase; 81, 90, 55, and 46 received 0, 1, 2, and 3 retreatments, respectively. The mean percentage decrease in NPRS score from baseline to weeks 2 to 12 after the final treatment was similar in patients receiving single or multiple NGX-4010 treatments (-25.8%, -27.1%, -24.6%, and -22.7% for 1, 2, 3, and 4 NGX-4010 treatments, respectively). PGIC and CGIC results demonstrated a benefit of NGX-4010 treatment through to the end of the study regardless of the number of treatments received. Transient local application site reactions were the most frequently reported adverse events, and were mainly mild to moderate, nonserious, and did not increase with repeated treatment.
Repeated NGX-4010 treatments were generally well tolerated and resulted in consistent reductions in HIV-DSP-associated pain and improvement in patient-reported outcomes.
To describe the comparison of multiple and single pain ratings in patients with complex regional pain syndrome type I (CRPS I).
Correlation, agreement, and reliability analyses were performed between the average pain intensity measured 3 times a day over a course of 4 days and one single pain rating (designated the "recalled average" pain, as assessed by the patient) before treatment and at 1-, 3-, and 6-month periods after treatment.
The patient population consisted of 54 patients with CRPS I in a randomized trial.
The results show that both measurements correlate and have excellent agreement. Furthermore, both ratings measure significant pain reduction after treatment; "recalled average" pain, however, reflects greater change in pain intensity.
In patients with CRPS I a single pain rating is an accurate predictor of the average pain measured by a multiple pain-rating test. Moreover, both assessments are accurate enough to determine changes in pain over time with an effective treatment.
The aim of this study was to examine whether the intensity of dynamic mechanical allodynia and spontaneous ongoing pain in patients with neuropathic pain associated with peripheral neuropathy was influenced by an intravenous infusion of the 5HT3-antagonist, ondansetron.
A randomized, double-blind, and placebo-controlled single intravenous infusion of 8 mg ondansetron or saline was administered to 15 patients during 10 minutes on 2 different occasions with an interval of at least 3 days. To monitor the brush-evoked allodynic percept over time, a computerized visual analog scale (VAS) was used allowing the patient to continuously rate the intensity and duration of pain. The area under the VAS curve was used to calculate the total brush-evoked pain intensity. Ongoing pain was rated using a VAS before each assessment of dynamic mechanical allodynia, that is, before and immediately after the infusion and at every 15 minutes over a period of 3 hours.
There was no influence of the factors with or without pain medication and treatment sequence (ie, ondansetron/saline or saline/ondansetron) on brush-evoked or ongoing pain intensity. No significant change over time was found after the infusion of either ondansetron or saline in the total brush-evoked pain intensity, in duration and frequency of aftersensation or in ongoing pain intensity.
No influence from 8 mg of ondansetron could be shown on the intensity of brush-evoked or spontaneous ongoing pain in patients with peripheral neuropathy, indicating the lack of involvement of 5HT3-receptors in an earlier proposed spinobulbospinal loop with descending facilitation acting on spinal mechanisms related to dynamic mechanical allodynia.