Even though pain is a subjective phenomenon, its objective evaluation in humans is important because subjects requiring pain evaluation may be unable to describe their pain intensity because of decreased awareness or impaired cognitive function. Previous reports indicate that the perfusion index (PI), which is calculated from pulse oximeter waveforms, has some utility in assessing pain. However, age-associated and sex-associated differences in change of PI have hitherto not been evaluated for assessment of pain. Therefore, we aimed to estimate the utility of age-related differences in PI change among healthy volunteers subjected to electrical stimulation.
We measured PI and pulse rate in 70 healthy volunteers exposed to gradually increasing electrical stimulation. The subjects were classified into four groups, ie, young men, young women, aged men, and aged women. Stimulation was stopped when subjects reached their pain tolerance threshold. The average PI and pulse rate were calculated 10 seconds before and after electrical stimulation and compared across the four groups. Changes in PI and pulse rate were analyzed using the paired t-test.
The PI was significantly decreased in response to pain stimulation in young men (P<0.0001), young women (P=0.0002), and aged men (P=0.0158). However, aged women failed to show significant changes in PI before or after stimulation. The pulse rate was not significantly altered in any of the groups.
PI may be an independent parameter reflecting the perception of noxious stimuli and could be used for objective evaluation of pain perception in healthy volunteers, except when it is used for pain evaluation in elderly women.
noxious stimuli; perfusion index; objective evaluation; age difference; sex difference
In patients, the perception of pain intensity may be influenced by the subjective representation of their disease. Although both multiple sclerosis (MS) and fibromyalgia (FM) possibly include chronic pain, they seem to elicit different disease representations because of the difference in their respective etiology, the former presenting evidence of underlying lesions as opposed to the latter. Thus, we investigated whether patients with FM differed from patients with MS with respect to their perception of “own” pain as well as others’ pain. In addition, the psychological concomitant factors associated with chronic pain were considered. Chronic pain patients with FM (n=13) or with MS (n=13) participated in this study. To assess specific pain-related features, they were contrasted with 12 other patients with MS but without chronic pain and 31 controls. A questionnaire describing imaginary painful situations showed that FM patients rated situations applied to themselves as less painful than did the controls. Additionally, pain intensity attributed to facial expressions was estimated as more intense in FM compared with the other groups of participants. There is good evidence that the mood and catastrophizing reactions expressed in FM differentially modulated the perception of pain according to whether it was their own pain or other’s pain.
chronic pain; self and other’s perspective; imaginary pain; facial expression
Chronic pain represents a major medical burden not only in terms of suffering but also in terms of economic costs. Traditional medical approaches have so far proven insufficient in treating chronic pain and new approaches are necessary. Gene therapy with herpes simplex virus (HSV)-based vectors offers the ability to directly target specific regions of the neuraxis involved in pain transmission including the primary afferent nociceptor. This opens up new targets to interact with that are either not available to traditional systemic drugs or cannot be adequately acted upon without substantial adverse off-target effects. Having access to the entire neuron, which HSV-based vector gene therapy enables, expands treatment options beyond merely treating symptoms and allows for altering the basic biology of the nerve. In this paper, we discuss several HSV-based gene therapy vectors that our group and others have used to target specific neuronal functions involved in the processing of nociception in order to develop new therapies for the treatment of chronic pain.
pain; gene therapy; herpes simplex virus; opioids; voltage-gated sodium channels; inhibitory neurotransmitters
In recent years, intravenously (IV) administered acetaminophen has become one of the most common perioperative analgesics. Despite its now-routine use, IV acetaminophen’s analgesic comparative efficacy has never been compared with that of ketamine, a decades-old analgesic familiar to obstetricians, gynecologists, and anesthesiologists alike. This doubleblind clinical trial aimed to evaluate the analgesic effects of ketamine and IV acetaminophen on postoperative pain after abdominal hysterectomy.
Eighty women aged 25–70 years old and meeting inclusion and exclusion criteria were randomly allocated into two groups of 40 to receive either IV acetaminophen or ketamine intraoperatively. Postoperatively, each patient had patient-controlled analgesia. Pain and sedation (Ramsay Sedation Scale) were documented based on the visual analog scale in the recovery room and at 4 hours, 6 hours, 12 hours, and 24 hours after the surgery. Hemodynamic changes, adverse medication effects, and the need for breakthrough meperidine were also recorded for both groups. Data were analyzed by repeated-measures analysis of variance.
Visual analog scale scores were significantly lower in the IV acetaminophen group at each time point (P<0.05), and this group required significantly fewer doses of breakthrough analgesics compared with the ketamine group (P=0.039). The two groups had no significant differences in terms of adverse effects.
Compared with ketamine, IV acetaminophen significantly improved postoperative pain after abdominal hysterectomy.
intravenous acetaminophen; abdominal hysterectomy; ketamine; analgesia; postoperative pain
Hemorrhoids are one of the most common ailments known. Often described as “varicose veins of the anus and rectum”, hemorrhoids are enlarged, bulging blood vessels in, and about the anus and lower rectum. About 75% of people will have hemorrhoids at some point in their lives. This paper shares the results from the clinical evaluation conducted to study effects of cryotherapy in treating uncomplicated hemorrhoids. The device used in the study is based on topically-applied cold therapy which can produce vasoconstriction in the tissues, tissue hypoxia, analgesia, and muscle relaxation. Cryotherapy was shown to be statistically similar or superior to proctology ointment in some of the parameters studied such as reduction of pain and hemorrhage. Overall it was observed that cryotherapy device contributes to improving the quality of life of patients with hemorrhoids.
cryotherapy; hemorrhage; hemorrhoids; analgesic
No proof of efficacy, in the form of a randomized controlled trial (RCT), exists to support pulsed radiofrequency (PRF) treatment of the dorsal root ganglion (DRG) for chronic lumbar radicular (CLR) pain. We determined the feasibility of a larger trial (primary objective), and also explored the efficacy of PRF in decreasing pain on a visual analog scale (VAS) and improving the Oswestry Disability Index.
This was a single-center, placebo-controlled, triple-blinded RCT. Patients were randomized to a placebo group (needle placement) or a treatment group (PRF at 42°C for 120 seconds to the DRG). Patients were followed up for 3 months post procedure. Outcomes with regard to pain, Oswestry Disability Index score, and side effects were analyzed on an intention-to-treat basis.
Over 15 months, 350 potential patients were identified and 56 were assessed for eligibility. Fifteen of them did not meet the selection criteria. Of the 41 eligible patients, 32 (78%) were recruited. One patient opted out before intervention. Three patients were lost to follow-up at 3 months. Mean VAS differences were not significantly different at 4 weeks (−0.36, 95% confidence interval [CI], −2.29, 1.57) or at 3 months (−0.76, 95% CI, −3.14, 1.61). The difference in mean Oswestry Disability Index score was also not significantly different at 4 weeks (−2%, 95% CI, −14%, 10%) or 3 months (−7%, 95% CI, −21%, 6%). There were no major side effects. Six of 16 patients in the PRF group and three of 15 in the placebo group showed a >50% decrease in VAS score.
The recruitment rate was partially successful. At 3 months, the relative success of PRF-DRG was small. A large-scale trial to establish efficacy is not practically feasible considering the small effect size, which would necessitate recruitment of a challengingly large number of participants over a number of years. Until clear parameters for application of PRF are established, clinicians will need to use their individual judgment regarding its clinical applicability, given the present evidence.
pulsed radiofrequency; radicular pain; dorsal root ganglion
To compare health care utilization of duloxetine initiators and pregabalin initiators among fibromyalgia patients in a real-world setting.
A retrospective cohort study was conducted based on a US national commercial health claims database (2006–2009). Fibromyalgia patients who initiated duloxetine or pregabalin in 2008, aged 18–64 years, and who maintained continuous health insurance coverage 1 year before and 1 year after initiation were assigned to duloxetine or pregabalin cohorts on the basis of their initiated agent. Patients who had pill coverage of the agents over the course of 90 days preceding the initiation were excluded. The two comparative cohorts were constructed using propensity score greedy match methods. Descriptive analysis and paired t-test were performed to compare health care utilization rates in the postinitiation year and the changes of these rates from the preinitiation year to the postinitiation year.
Both matched cohorts (n=1,265 pairs) had a similar mean initiation age (49–50 years), percentage of women (87%–88%), and prevalence of baseline comorbid conditions (neuropathic pain other than diabetic peripheral neuropathic pain, low back pain, cardiovascular disease, hypertension, headache or migraine, and osteoarthritis). In the preinitiation year, both cohorts had similar inpatient, outpatient, and medication utilization rates (inpatient, 15.7%–16.1%; outpatient, 100.0%; medication, 97.9%–98.7%). The utilization rates diverged in the postinitiation year, with the pregabalin cohort using more fibromyalgia-related inpatient care (3.2% versus 2.2%; P<0.05), any inpatient care (19.3% versus 16.8%; P<0.05), and fibromyalgia-related outpatient care (62.1% versus 51.8%; P<0.05). From the preinitiation period to the postinitiation period, the duloxetine cohort experienced decreases in certain utilization rates, whereas the pregabalin cohort had increases (percentage of patients with a fibromyalgia-related admission, −1.2% versus 0.4% [P<0.01]; number of fibromyalgia-related outpatient claims, −1.7 versus 4.7 [P<0.01]).
Fibromyalgia patients initiating pregabalin tended to consume more fibromyalgia-related inpatient and outpatient care in the first postinitiation year, whereas fibromyalgia patients initiating duloxetine tended to have lower utilization rates of fibromyalgia-related inpatient care in the postinitiation year than in the preinitiation year.
fibromyalgia; health care utilization; propensity score methods; duloxetine; pregabalin
Carrageenan-induced arthritis is a painful acute arthritis model that is simple to induce, with peak pain and inflammation occurring at about 3 hours. This arthritis model can be evaluated using semiquantitative evoked or non-evoked pain scoring systems. These measures are subjective and are often time- and labor-intensive. It would be beneficial to utilize quantitative, nonsubjective evaluations of pain with rapid assessment tools. We sought to compare the DigiGait™ and TreadScan™ systems and to validate the two gait analysis platforms for detection of carrageenan-induced monoarthritis pain and analgesic response through changes in gait behavior.
Non-arthritic mice and carrageenan-induced arthritic mice with and without analgesia were examined. A painful arthritic knee was produced by injection of 3% carrageenan into the knee joint of adult mice. Analgesic-treated mice were injected subcutaneously with 0.015 mg/mL (0.5 mg/kg) buprenorphine. Five-second videos were captured on the DigiGait™ or TreadScan™ system and, after calculating gait parameters, were compared using student’s unpaired t-test.
We found the DigiGait™ system consistently measured significantly longer stride measures (swing time, stance time, and stride time) than did TreadScan™. Both systems’ measures of variability were equal. Reproducibility was inconsistent on both systems. While both systems detected alterations in some gait measures after carrageenan injection, none of the alterations were seen with both systems. Only the TreadScan™ detected normalization of gait measures after analgesia, but the system could not detect normalization across all measures that altered due to arthritis pain. Time spent on analysis was dependent on operator experience.
Neither the DigiGait™ nor TreadScan™ system was useful for measuring changes in pain behaviors or analgesic responses in acute inflammatory monoarthritic mice.
arthritis; mouse; video
While the validity of pain assessment has been well documented, the underlying schema (ie, organized, preconceived ideas) of how individuals interpret numerical pain ratings is not well understood. This study’s objectives were to examine numerical pain intensity ratings, from (0 to 10 cm on the visual analog scale [VAS]) across multiple severities of commonly experienced acute pain conditions to determine whether the ratings differed between these pain conditions and/or between individuals.
A community sample (N=365, 66% female) rated their anticipated pain intensity (VAS) for threshold, mild, moderate, severe, and tolerance level, using several common pain conditions: headache, toothache, joint injury, delayed-onset muscle soreness, burns, and “general pain.”
Cluster analysis revealed three subgroups of individuals, suggesting three types of underlying pain rating schema: 1) Low Rating subgroup (low VAS pain intensity ratings across all the pain severity categories); 2) Low/High Rating subgroup (low VAS pain intensity rating for mild, but high VAS pain intensity rating for severe pain); and 3) High Rating subgroup (high VAS pain intensity ratings across all the pain severity categories). Overall, differences between pain conditions were small: muscle soreness pain intensity was consistently rated lower than the other pain types across severities. The highest pain ratings varied between joint injury and general pain, depending on severity level. No effects of sex or current experience of pain were noted.
The results indicate that: 1) three distinct pain schemas were present in this community-based sample, indicating significant variation in how pain scales are utilized and/or interpreted between clusters of individuals; 2) pain ratings vary by condition, but these differences are minor; and 3) pain rating schemas are not significantly different between males and females or between individuals with and without current pain.
VAS; muscle soreness; headache; toothache; joint pain
The treatment of central neuropathic pain remains amongst the biggest challenges for pain specialists. The main objective of this study was to assess gabapentin (GBP), amitriptyline (AMI), and carbamazepine (CARBA) for the treatment of a rodent central neuropathic pain model.
Male Sprague Dawley rats were trained on the rotarod, Hargreaves, Von Frey and acetone behavioral tests, and baseline values were obtained prior to surgery. A stereotaxic injection of either a collagenase solution or saline was made in the right ventral posterolateral thalamic nucleus. The rats were tested on days 2, 4, 8, and 11 postsurgery. They were retested at regular intervals from day 15 to day 25 postsurgery, after oral administration of either the vehicle (n=7 and n=8 rats with intracerebral injections of collagenase and saline, respectively) or the different drugs (GBP [60 mg/kg], AMI [10 mg/kg], CARBA [100 mg/kg]; n=8 rats/drug).
A significant decrease in the mechanical thresholds and no change in heat threshold were observed in both hind limbs in the collagenase group, as we had previously shown elsewhere. Reversal of the mechanical hypersensitivity was achieved only with GBP (P<0.05). AMI and CARBA, at the dosages used, failed to show any effect on mechanical thresholds. Transient cold allodynia was observed in some collagenase-injected rats but failed to be statistically significant.
Intrathalamic hemorrhaging in the ventrolateral thalamic nucleus induced a bilateral mechanical allodynia, which was reversed by GBP but not AMI or CARBA.
central pain; thalamus; amitriptyline; carbamazepine
Studies report the need for improved pain management in the radiation oncology setting. Many patients with well controlled background pain experience breakthrough pain in cancer (BTPc) that can interrupt their treatment schedule with a potentially negative impact on outcomes. BTPc can be unpredictable and predictable; both types of pain can be managed with fast-acting analgesics, but predictable pain lends itself to anticipatory management.
Five consecutive cases are described in which fentanyl pectin nasal spray (FPNS) was used to manage BTPc, with an emphasis on the anticipatory management of predictable pain in cancer patients receiving radiotherapy.
Patients (four men, one woman), age range 32–84 years, were diagnosed with various cancers. All patients were receiving opioid treatment for chronic pain, and experienced predictable pain with radiotherapy which included pain associated with lying on a treatment table for a sustained time during an average of 29 radiotherapy treatments; pain associated with radiation simulation and radiotherapy; pain associated with odynophagia related to increasing mucositis during treatment, resulting in decreased nutritional intake; pain associated with the customized immobilization mask for head and neck cancer patients; and pain associated with defecation. Some patients also reported pain awakening them randomly at night (eg, sleep interruption). All patients attained lower pain intensity scores (2/10 to 3/10), reduced from approximately 7/10, when they were treated with FPNS 20 minutes before a predictable pain event. No patient experienced any pain-related interruptions to their course of radiotherapy. The average number of radiotherapy sessions was 29 per patient, excluding one short-course treatment for one patient.
FPNS offers a good solution to the management of BTPc because its fast onset of action makes it very suitable for the anticipatory treatment of predictable pain, which is likely to minimize interruptions to the radiotherapy schedule.
radiotherapy; predictable pain; fentanyl pectin nasal spray; interruption of treatment
Lumbar radiculopathy pain represents a major public health problem, with few effective long-term treatments. Preclinical neuropathic and postsurgical pain studies implicate the kinase adenosine monophosphate activated kinase (AMPK) as a potential pharmacological target for the treatment of chronic pain conditions. Metformin, which acts via AMPK, is a safe and clinically available drug used in the treatment of diabetes. Despite the strong preclinical rationale, the utility of metformin as a potential pain therapeutic has not yet been studied in humans. Our objective was to assess whether metformin is associated with decreased lumbar radiculopathy pain, in a retrospective chart review. We completed a retrospective chart review of patients who sought care from a university pain specialist for lumbar radiculopathy between 2008 and 2011. Patients on metformin at the time of visit to a university pain specialist were compared with patients who were not on metformin. We compared the pain outcomes in 46 patients on metformin and 94 patients not taking metformin therapy. The major finding was that metformin use was associated with a decrease in the mean of “pain now,” by −1.85 (confidence interval: −3.6 to −0.08) on a 0–10 visual analog scale, using a matched propensity scoring analysis and confirmed using a Bayesian analysis, with a significant mean decrease of −1.36 (credible interval: −2.6 to −0.03). Additionally, patients on metformin showed a non-statistically significant trend toward decreased pain on a variety of other pain descriptors. Our proof-of-concept findings suggest that metformin use is associated with a decrease in lumbar radiculopathy pain, providing a rational for larger retrospective trials in different pain populations and for prospective trials, to test the effectiveness of metformin in reducing neuropathic pain.
neuropathy; mTOR; adenosine monophosphate activated kinase; diabetes
Chronic pain is highly prevalent in the United States and Canada, occurring in an estimated 30% of the adult population. Despite its high prevalence, US and Canadian medical schools provide very little training in pain management, including training in the safe and effective use of potent analgesics, most notably opioids. In 2005, the International Association for the Study of Pain published recommendations for a core undergraduate pain management curriculum, and several universities have implemented pilot programs based on this curriculum. However, when outcomes have been formally assessed, these initiatives have resulted in only modest improvements in physician knowledge about chronic pain and its treatment. This article discusses strategies to improve undergraduate pain management curricula and proposes areas in which those efforts can be augmented. Emphasis is placed on opioids, which have great potency as analgesics but also substantial risks in terms of adverse events and the risk of abuse and addiction. The authors conclude that the most important element of an undergraduate pain curriculum is clinical experience under mentors who are capable of reinforcing didactic learning by modeling best practices.
chronic pain; curricular content; medical education; opioids; pain education; pain knowledge; physician training; teaching
The transversus abdominis plane (TAP) block is a technique increasingly used for analgesia after surgery on the anterior abdominal wall. We undertook this study to determine the feasibility and analgesic efficacy of ultrasound-guided TAP blocks in morbidly obese patients. We describe the dermatomal spread of local anesthetic in TAP blocks administered, and test the hypothesis that TAP blocks decrease visual analog scale (VAS) scores.
Patients and methods
After ethics committee approval and informed consent, 35 patients with body mass index >35 undergoing single-port sleeve gastrectomy (SPSG) were enrolled. All patients received balanced general anesthesia, followed by intravenous patient-controlled analgesia (IV-PCA; hydromorphone) postoperatively; all reported VAS >3 upon arrival to the recovery room. From the cohort of 35 patients having single-port laparoscopy (SPL), a sealed envelope method was used to randomly select ten patients to the TAP group and 25 patients to the control group. The ten patients in the TAP group received ultrasound-guided TAP blocks with 30 mL of 0.2% Ropivacaine injected bilaterally. The dermatomal distribution of the sensory block (by pinprick test) was recorded. VAS scores for the first 24 hours after surgery and opioid use were compared between the IV-PCA+TAP block and IV-PCA only groups.
Sensory block ranged from T5–L1. Mean VAS pain scores decreased from 8 ± 2 to 4 ± 3 (P=0.04) within 30 minutes of TAP block administration. Compared with patients given IV-PCA only, significantly fewer patients who received TAP block had moderate or severe pain (VAS 4–10) after block administration at 6 hours and 12 hours post-surgery. However, cumulative consumption of hydromorphone at 24 hours after SPSG surgery was similar for both groups.
Ultrasound-guided TAP blocks in morbidly obese patients are feasible and result in satisfactory analgesia following SPSG in the immediate postoperative period.
regional anesthesia; postoperative pain; ultrasound; analgesia; nerve blocks
To describe the use of pain medications in patients with chronic low back pain (CLBP) after initiating duloxetine or standard of care (SOC [muscle relaxants, gabapentin, pregabalin, venlafaxine, and tricyclic antidepressants]) for pain management, pharmacy and medical claims from Surveillance Data, Inc (SDI) Health were analyzed. Adult patients with CLBP who initiated duloxetine or SOC between November 2010 and April 2011 were identified. Treatment initiation was defined as no pill coverage for duloxetine or SOC in the previous 90 days. Included patients had no opioid use in the 90 days before initiation. Propensity score matching was used to select patients with similar baseline demographic and clinical characteristics for duloxetine and SOC cohorts. Compliance with index medication was assessed via medication possession ratio (MPR) and proportion of days covered (PDC) for 6 months after initiation. The proportion of patients receiving opioids and days on opioids after index date were assessed, and regression models were estimated to compare opioid use between cohorts. A total of 766 patients initiated duloxetine and 6,206 patients initiated SOC. After matching, 743 patients were selected for the duloxetine (mean age 57 years; female 74%) and SOC (mean age 57 years; female 75%) cohorts, respectively. Of the duloxetine cohort, 92% started on or below recommended daily dose (≤60 mg). The duloxetine cohort had significantly higher MPR (0.78 versus [vs] 0.60) and PDC (0.50 vs 0.31), were less likely to use opioids (45% vs 61%), and had fewer days on opioids (median 0 vs 7 days) than the SOC cohort (all P < 0.001). After adjusting for demographic and clinical characteristics, the duloxetine cohort initiated opioids later than the SOC cohort (hazard ratio 0.77, 95% confidence interval 0.66–0.89). CLBP patients initiating duloxetine had better compliance with initiated medication and were less likely to use opioids than those initiating SOC.
medications; duloxetine; low back pain; opioid
Electroencephalography (EEG) may be a promising source of physiological biomarkers accompanying chronic pain. Several studies in patients with chronic neuropathic pain have reported alterations in central pain processing, manifested as slowed EEG rhythmicity and increased EEG power in the brain’s resting state. We aimed to investigate novel potential markers of chronic pain in the resting state EEG of patients with chronic pancreatitis.
Resting state EEG data from 16 patients with persistent abdominal pain due to chronic pancreatitis (CP) were compared to data from healthy controls matched for age, sex and education.
The peak alpha frequency (PAF) and power amplitude in the alpha band (7.5–13 Hz) were compared between groups in four regions of interest (frontal, central, parietal, and occipital) and were correlated with pain duration.
The average PAF was lowered in CP patients compared with that in healthy controls, observed as a statistically significant between-group effect (mean 9.9 versus 9.5 Hz; P=0.049). Exploratory post hoc analysis of average PAF per region of interest revealed a significant difference, particularly in the parietal and occipital regions. In addition, we observed a significant correlation between pain duration and PAF and showed increased shifts in PAF with longer pain durations. No significant group differences were found in peak power amplitudes.
CP pain is associated with alterations in spontaneous brain activity, observed as a shift toward lower PAF. This shift correlates with the duration of pain, which demonstrates that PAF has the potential to be a clinically feasible biomarker for chronic pain. These findings could be helpful for assisting diagnosis, establishing optimal treatment, and studying efficacy of new therapeutic agents in chronic pain patients.
chronic pain; neuropathic pain; chronic pancreatitis; electroencephalography; EEG; alpha oscillations; peak frequency
Neuropathic pain represents a major problem in clinical medicine because it causes debilitating suffering and is largely resistant to currently available analgesics. A characteristic of neuropathic pain is abnormal response to somatic sensory stimulation. Thus, patients suffering peripheral neuropathies may experience pain caused by stimuli which are normally nonpainful, such as simple touching of the skin or by changes in temperature, as well as exaggerated responses to noxious stimuli. Convincing evidence suggests that this hypersensitivity is the result of pain remaining centralized. In particular, at the first pain synapse in the dorsal horn of the spinal cord, the gain of neurons is increased and neurons begin to be activated by innocuous inputs. In recent years, it has become appreciated that a remote damage in the peripheral nervous system results in neuronal plasticity and changes in microglial and astrocyte activity, as well as infiltration of macrophages and T cells, which all contribute to central sensitization. Specifically, the release of pronociceptive factors such as cytokines and chemokines from neurons and non-neuronal cells can sensitize neurons of the first pain synapse. In this article we review the current evidence for the role of cytokines in mediating spinal neuron–non-neuronal cell communication in neuropathic pain mechanisms following peripheral nerve injury. Specific and selective control of cytokine-mediated neuronal–glia interactions results in attenuation of the hypersensitivity to both noxious and innocuous stimuli observed in neuropathic pain models, and may represent an avenue for future therapeutic intervention.
anti-inflammatory cytokines; proinflammatory cytokines; microglia; astrocytes; first pain synapse
Chronic pain in children and adolescents is a growing problem and one that is increasingly being addressed with multidisciplinary treatment teams. This review summarizes different multidisciplinary clinics, focusing specifically on intensive pediatric pain rehabilitation centers. This review offers a summary of the challenges faced by these programs and areas for future study.
pediatric pain rehabilitation; pediatric chronic pain; interdisciplinary; pain associated disability
Heat/capsaicin skin sensitization is a well-characterized human experimental model to induce hyperalgesia and allodynia. Using this model, gabapentin, among other drugs, was shown to significantly reduce cutaneous hyperalgesia compared to placebo. Since the larger thermal probes used in the original studies to produce heat sensitization are now commercially unavailable, we decided to assess whether previous findings could be replicated with a currently available smaller probe (heated area 9 cm2 versus 12.5–15.7 cm2).
Study design and methods
After Institutional Review Board approval, 15 adult healthy volunteers participated in two study sessions, scheduled 1 week apart (Part A). In both sessions, subjects were exposed to the heat/capsaicin cutaneous sensitization model. Areas of hypersensitivity to brush stroke and von Frey (VF) filament stimulation were measured at baseline and after rekindling of skin sensitization. Another group of 15 volunteers was exposed to an identical schedule and set of sensitization procedures, but, in each session, received either gabapentin or placebo (Part B).
Unlike previous reports, a similar reduction of areas of hyperalgesia was observed in all groups/sessions. Fading of areas of hyperalgesia over time was observed in Part A. In Part B, there was no difference in area reduction after gabapentin compared to placebo.
When using smaller thermal probes than originally proposed, modifications of other parameters of sensitization and/or rekindling process may be needed to allow the heat/capsaicin sensitization protocol to be used as initially intended. Standardization and validation of experimental pain models is critical to the advancement of translational pain research.
experimental pain model; hyperalgesia; peripheral sensitization; central sensitization
Up to 80% of patients with severe posttraumatic stress disorder are suffering from “unexplained” chronic pain. Theories about the links between traumatization and chronic pain have become the subject of increased interest over the last several years. We will give a short summary about the existing interaction models that emphasize particularly psychological and behavioral aspects of this interaction. After a synopsis of the most important psychoneurobiological mechanisms of pain in the context of traumatization, we introduce the hypermnesia–hyperarousal model, which focuses on two psychoneurobiological aspects of the physiology of learning. This hypothesis provides an answer to the hitherto open question about the origin of pain persistence and pain sensitization following a traumatic event and also provides a straightforward explanatory model for educational purposes.
posttraumatic stress disorder; chronic pain; hypermnesia; hypersensitivity; traumatization
To evaluate the safety and efficacy of ketoprofen in Transfersome® gel (IDEA-033) in comparison with a ketoprofen-free vehicle (TDT 064) for the treatment of osteoarthritis (OA) of the knee.
Patients with knee OA (N = 866) were randomly assigned to receive topical IDEA-033 containing 100, 50, or 25 mg ketoprofen, or TDT 064 twice daily for 12 weeks, in a double-blind trial. The primary efficacy endpoint was the change in the Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index pain subscale score. The coprimary efficacy endpoints were the WOMAC function subscale score and the patient global assessment of response to therapy. The secondary endpoints included the numeric pain rating for the first 14 days of treatment and the Outcome Measures in Rheumatology (OMERACT)-Osteoarthritis Research Society International (OARSI) responder rates.
The WOMAC pain scores were reduced by approximately 50% or more in all four groups. The 100 and 50 mg ketoprofen groups, but not the 25 mg group, showed a superior reduction in the WOMAC pain score versus the TDT 064 group (100 mg: −57.4% [P = 0.0383]; 50 mg: −57.1% [P = 0.0204]; and 25 mg: −53.4% [P = 0.3616] versus TDT 064: −49.5%). The superiority of the ketoprofen-containing formulations was not demonstrated for the WOMAC function subscale score, whereas the patient global assessment of 50 mg ketoprofen group, but not the 100 or 25 mg group, was superior to that of the TDT 064 group (P = 0.0283). Responder rates were significantly higher for all the IDEA-033 groups versus the TDT 064 group, but were high in all groups (100 mg: 88.6%; 50 mg: 86.8%; 25 mg: 88.6%; and TDT 064: 77.5%). Dermal reactions were the only relevant drug-related adverse events in all four groups.
The 50 and 100 mg ketoprofen doses of IDEA-033 were only marginally superior to TDT 064 for reducing pain associated with knee OA. The study indicates a high treatment response to the topical ketoprofen-free vehicle TDT 064.
Sequessome™; pain; non-steroidal anti-inflammatory drugs; drug-free; medical device
The goal of this longitudinal study was to examine the associations among psychological factors and pain reports of children and their parents over the 12 month period after pediatric surgery.
Materials and methods
Included in the study were 83 children aged 8–18 years undergoing major surgery. In each case, the child and one of their parents completed measures of pain intensity and unpleasantness, psychological function, and functional disability at 48–72 hours, 2 weeks (child only), 6 months, and 12 months after surgery.
The strength of the correlation coefficients between the psychological measures of the parent and their child increased significantly over time. There was a fair level of agreement between parent ratings of child acute and chronic pain (6 months after surgery) and the child’s actual ratings. Parent and child pain anxiety scores 48–72 hours after surgery interacted significantly to predict pain intensity, pain unpleasantness, and functional disability levels 2 weeks after discharge from hospital. Parent pain catastrophizing scores 48–72 hours after surgery predicted child pain intensity reports 12 months later.
These results raise the possibility that as time from surgery increases, parents exert greater and greater influence over the pain response of their children, so that by 12 months postsurgery mark, parent pain catastrophizing (measured in the days after surgery) is the main risk factor for the development of postsurgical pain chronicity.
pain anxiety; pain catastrophizing; children; parental risk factors; postsurgical pain
Pain is an intricate phenomenon composed of not only sensory-discriminative aspects but also of emotional, cognitive, motivational, and affective components. There has been ample evidence for the existence of an extensive cortical network associated with pain processing over the last few decades. This network includes the anterior cingulate cortex, forebrain, insular cortex, ventrolateral orbital cortex, somatosensory cortex, occipital cortex, retrosplenial cortex, motor cortex, and prefrontal cortex. Diverse neurotransmitters participate in the cortical circuits associated with pain processing, including glutamate, gamma-aminobutyric acid, dopamine, and opioids. This work examines recent rodent studies about cortical modulation of pain, mainly at a molecular level.
pain; glutamate; glia; cingulate cortex; somatosensory cortex; insular cortex