Consistency of inconsistency in long-COVID-19 pain symptoms persistency: A systematic review and meta-analysis.

INTRODUCTION: Individuals recovering from acute COVID-19 episodes may continue to suffer from various ongoing symptoms, collectively referred to as Long-COVID. Long-term pain symptoms are amongst the most common and clinically significant symptoms to be reported for this post-COVID-19 syndrome. OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the proportions of persisting pain symptoms experienced by individuals past the acute phase of COVID-19 and to identify their associated functional consequences and inflammatory correlates. METHODS: Two online databases were systematically searched from their inception until 31 March 2022. We searched primary research articles in English, which evaluated individuals after laboratory-confirmed COVID-19 acute phase resolution and specifically reported on pain symptoms and their inflammatory and/or functional outcomes. RESULTS: Of the 611 identified articles, 26 were included, used for data extraction, and assessed for their methodological quality and risk of bias by two independent reviewers. Pain symptoms were grouped under one of six major pain domains, serving as our primary co-outcomes. Proportional meta-analyses of pooled logit-transformed values of single proportions were performed using the random-effects-restricted maximum-likelihood model. An estimated 8%, 6%, 18%, 18%, 17%, and 12% of individuals continued to report the persistence of chest, gastrointestinal, musculoskeletal joint, musculoskeletal muscle, general body, and nervous system-related pain symptoms, respectively, for up to one year after acute phase resolution of COVID-19. Considerable levels of heterogeneity were demonstrated across all results. Functional and quality-of-life impairments and some inflammatory biomarker elevations were associated with the persistence of long-COVID pain symptoms. CONCLUSION: This study's findings suggest that although not well characterized, long-COVID pain symptoms are being experienced by non-negligible proportions of those recovering from acute COVID-19 episodes, thus highlighting the importance of future research efforts to focus on this aspect.

[MEDICAL MARIJUANA DEPENDENCE AMONG CHRONIC PAIN PATIENTS SUFFERING FROM DEPRESSION AND ANXIETY].

INTRODUCTION: In recent years, medical marijuana (MM) is increasingly being used for the treatment of chronic pain. Depression and anxiety have been identified as risk factors for the problematic use of prescription opioids, yet their contribution to developing MM dependence hasn't been explored up to date. In this study we explored the association between depression and anxiety severity and the risk for cannabis dependence among chronic pain patients prescribed MM. METHODS: Participants were 324 chronic pain patients prescribed MM with no cuncurrent opioid treatment. All participants were screened for depression using the Patient Health Questionnaire (PHQ-9), for anxiety using the Generalized Anxiety Disorder questionnaire (GAD-7) and for problematic use of MM according to DSM-IV criteria for cannabis dependence using the AUDADI-IT questionnaire. Logistic regression analyses controlling for additional sociodemographic and clinical factors were conducted. RESULTS: Generally, prevalence of cannabis dependence was higher among participants with levels of depression and anxiety levels compared to those without depression or anxiety. However, after controlling for confounders only participants with severe depression were significantly more likely (Adjusted Odds Ratio=5.86) to screen positive for cannabis dependence compared to those without depression. CONCLUSIONS: Severe depression may be a risk factor for problematic use of MM among chronic pain patients. Increasing use of MM calls for further explotartion of potential risk factors which may predict problematic MM use among this population.

Problematic Use of Prescription Opioids and Medicinal Cannabis Among Patients Suffering from Chronic Pain.

Objective: To assess prevalence rates and correlates of problematic use of prescription opioids and medicinal cannabis (MC) among patients receiving treatment for chronic pain. Design: Cross-sectional study. Setting: Two leading pain clinics in Israel. Subjects: Our sample included 888 individuals receiving treatment for chronic pain, of whom 99.4% received treatment with prescription opioids or MC. Methods: Problematic use of prescription opioids and MC was assessed using DSM-IV criteria, Portenoy's Criteria (PC), and the Current Opioid Misuse Measure (COMM) questionnaire. Additional sociodemographic and clinical correlates of problematic use were also assessed. Results: Among individuals treated with prescription opioids, prevalence of problematic use of opioids according to DSM-IV, PC, and COMM was 52.6%, 17.1%, and 28.7%, respectively. Among those treated with MC, prevalence of problematic use of cannabis according to DSM-IV and PC was 21.2% and 10.6%, respectively. Problematic use of opioids and cannabis was more common in individuals using medications for longer periods of time, reporting higher levels of depression and anxiety, and using alcohol or drugs. Problematic use of opioids was associated with higher self-reported levels of pain, and problematic use of cannabis was more common among individuals using larger amounts of MC. Conclusions: Problematic use of opioids is common among chronic pain patients treated with prescription opioids and is more prevalent than problematic use of cannabis among those receiving MC. Pain patients should be screened for risk factors for problematic use before initiating long-term treatment for pain-control.

Cancer pain patients do not successfully handle opioids.

OBJECTIVE: To evaluate patterns of opioid handling as well as their associated -variables. DESIGN: A transversal study. SETTING: Institutional care. PARTICIPANTS: One hundred cancer pain patients aged 18 and above at diagnosis. INTERVENTIONS: Open and dichotomous questions related to opioid handling and a depression-anxiety scale. MAIN OUTCOME MEASURE(S): The percentage of patients who properly handled opioids. RESULTS: Of those surveyed, 42.1 percent of patients reported receiving opioid storage instructions, 73 percent did not receive any instructions related to proper opioid return/disposal, and 39 percent wrongly discarded them. The mean of patients with anxiety symptoms was 6.95 and of depression symptoms was 8.19. The Hebrew Version of the Hospital and Anxiety Scale total mean was 15.1. A significant relationship among patients with poor disposal habits was also found. CONCLUSIONS: Despite being aware of opioid's danger, patients' attitudes evidenced a poor safety responsibility. We believe that this might be due to the high percentage of disinformation and the influence of psychological symptoms on patients' decision-making.

Long-term safety of spinal cord stimulation systems in a prospective, global registry of patients with chronic pain.

Aim: The availability of long-term (>2 years) safety outcomes of spinal cord stimulation (SCS) remains limited. We evaluated safety in a global SCS registry for chronic pain. Methods: Participants were prospectively enrolled globally at 79 implanting centers and followed out to 3 years after device implantation. Results: Of 1881 participants enrolled, 1289 received a permanent SCS implant (1776 completed trial). The annualized rate of device explant was 3.5% (all causes), and 1.1% due to inadequate pain relief. Total incidence of device explantation >3 years was 7.6% (n = 98). Of these, 32 subjects (2.5%) indicated inadequate pain relief as cause for removal. Implant site infection (11 events) was the most common device-related serious adverse event (<1%). Conclusion: This prospective, global, real-world study demonstrates a high-level of safety for SCS with low rate of explant/serious adverse events. Clinical Trial Registration: NCT01719055 (ClinicalTrials.gov).

The effects of TENS, interferential stimulation, and combined interferential stimulation and pulsed ultrasound on patients with disc herniation-induced radicular pain.

BACKGROUND: Electrotherapy is part of a physician's toolbox for treating various musculoskeletal conditions, including radicular pain, but the preferred modality is yet unclear. OBJECTIVE: To compare the short-term efficacy of three electrotherapeutic modalities in relieving lumbar disc herniation (LDH)-induced radicular pain. METHODS: Fourteen patients with LDH-induced radicular pain attended a single session of electrotherapy, which included four 10-min consecutive treatments: transcutaneous electrical nerve stimulation (TENS), interferential (IF) stimulation, a combined treatment with pulsed ultrasound and IF current (CTPI), and a sham control. Treatments were randomized and the straight leg raise (SLR) degree was measured immediately before and after each treatment. RESULTS: Each of the three active modalities significantly improved the SLR score. The most prominent improvement was observed in the CTPI condition, followed by IF and, finally, TENS. The sham stimulation did not affect the SLR scores. CONCLUSIONS: A single session with either TENS, IF current or CTPI is sufficient to improve the range of motion and degree of radicular pain associated with LDH. CTPI appears to be the most effective modality of the three, possibly due to greater penetration efficiency of the induced current. The effects of a long-term treatment schedule are yet to be identified.

Attitudes Toward the Use of Medical Cannabis and the Perceived Efficacy, Side-effects and Risks: A Survey of Patients, Nurses and Physicians.

Gaps between physician and patient perceptions may lead to misunderstandings and mismanage of treatment. There are sparse data about the differences in opinions toward medical cannabis (MC) between patients and health professionals. The aim of this study was to examine the attitudes toward MC, its perceived efficacy, side effects and risk of dependency, among patients, nurses and physicians. A cross-sectional study of samples of 430 patients, 65 nurses and 65 physicians in two large medical centers in Israel. Questionnaires were administered on attitudes, perceived efficacy, side-effects and perceived risks of dependency. Compared with nurses and physicians, patients who were using MC had the most positive attitudes toward MC (p < .001). Younger age, high school education, being Jewish and ever using MC, were associated with more positive attitudes toward MC among patients (p < .001). Among nurses and physicians, having an oncology specialty predicted more positive attitudes toward MC. Physicians had a less positive attitude toward MC compared to nurses (p < .01). Our study provides evidence that physicians are less positive in their views toward MC compared to nurses and patients. More information and awareness to MC may reduce the gap in perceptions between physicians and patients.

Medical cannabis treatment for chronic pain: Outcomes and prediction of response.

BACKGROUND: Although studied in a few randomized controlled trials, the efficacy of medical cannabis (MC) for chronic pain remains controversial. Using an alternative approach, this multicentre, questionnaire-based prospective cohort was aimed to assess the long-term effects of MC on chronic pain of various aetiologies and to identify predictors for MC treatment success. METHODS: Patients with chronic pain, licensed to use MC in Israel, reported weekly average pain intensity (primary outcome) and related symptoms before and at 1, 3, 6, 9 and 12 months following MC treatment initiation. A general linear model was used to assess outcomes and identify predictors for treatment success (≥30% reduction in pain intensity). RESULTS: A total of 1,045 patients completed the baseline questionnaires and initiated MC treatment, and 551 completed the 12-month follow-up. At 1 year, average pain intensity declined from baseline by 20% [-1.97 points (95%CI = -2.13 to -1.81; p < 0.001)]. All other parameters improved by 10%-30% (p < 0.001). A significant decrease of 42% [reduction of 27 mg; (95%CI = -34.89 to 18.56, p < 0.001)] from baseline in morphine equivalent daily dosage of opioids was also observed. Reported adverse effects were common but mostly non-serious. Presence of normal to long sleep duration, lower body mass index and lower depression score predicted relatively higher treatment success, whereas presence of neuropathic pain predicted the opposite. CONCLUSIONS: This prospective study provides further evidence for the effects of MC on chronic pain and related symptoms, demonstrating an overall mild-to-modest long-term improvement of the tested measures and identifying possible predictors for treatment success.

Depression level, not pain severity, is associated with smoked medical marijuana dosage among chronic pain patients.

BACKGROUND: The use of medical marijuana (MM) for the treatment of chronic pain is rapidly growing in the United States and Europe; however there is concern regarding the specificity of its therapeutic effects and the motivation underlying its use. While research indicates that among chronic pain prescribed opioids, depression has been associated with increased opioid dosage (regardless of pain levels), the extent to which depression and pain each contribute to MM dose among chronic pain patients is yet unknown. METHODS: This cross-sectional study included 209 chronic pain patients prescribed smoked MM, in flower or other plant form, with no concurrent opioid treatment. Ordinal regression analyses were performed in order to explore the unique contribution of mean pain level (1-10 scale), depression severity (measured by the Patient Health Questionnaire (PHQ-9)) and anxiety severity (measured by the Generalized Anxiety Disorder scale (GAD-7)) to doses of MM, while taking into account additional sociodemographic and clinical factors. RESULTS: Individuals with mild depression and those with moderate to severe depression were at significantly increased odds for using higher doses of MM in grams per month(Adjusted Odds Ratio(AOR) = 2.06,95% Confidence Interval(CI) = 1.05-4.01, and AOR = 5.95,95% CI = 1.97-17.98, respectively) compared to those without depression. In addition, individuals with mild depression were at significantly increased odds for smoking more MM joints daily(AOR = 2.07, 95% CI = 1.01-4.23) compared to individuals without depression. Mean levels of pain or anxiety severity were not significantly associated with either dose measures. CONCLUSIONS: Depression and MM dose are highly correlated and should be concurrently addressed during chronic pain treatment.

Enhanced pain modulation capacity among individuals with borderline personality disorder: A possible mechanism underlying their hypoalgesia.

BACKGROUND: Ample evidence suggests that individuals with borderline personality disorder (BPD) exhibit hyposensitivity to pain. Since the underlying mechanism of the pain hyposensitivity is unknown, we tested here for the first time whether this hyposensitivity is pain specific or exists also for innocuous sensation, and whether it is associated with enhanced descending pain modulation capabilities. METHODS: Participants were 55 women; 22 patients with BPD and 33 matched healthy controls. Testing included the measurement of warmth sensation threshold (WST), heat-pain threshold (HPT), pain adaptation, conditioned pain modulation (CPM) and temporal summation of heat-pain (TSP). The level of dissociation was also evaluated. RESULTS: Women with BPD had higher WST and HPT compared with healthy controls. Moreover, women with BPD had greater magnitude of pain adaptation and CPM as well as higher dissociation level compared to controls. In neither the BPD nor the control group did WST and HPT correlate with pain adaptation, CPM or dissociation. In the BPD group only, HPT inversely correlated with the magnitude of TSP. CONCLUSIONS: Women with BPD present generalized hyposensitivity to both innocuous and noxious stimuli. Furthermore, women with BPD exhibit more efficient pain inhibition capabilities than healthy controls. While efficient pain modulation may underlie pain hyposensitivity in BPD, both traits may exist independently from each other, or may be moderated by another factor such as dissociation. SIGNIFICANCE: On the basis of testing pronociceptive and antinociceptive components among individuals with BPD and healthy controls, this study reveals enhanced ability to inhibit pain among woman with borderline personality disorder (BPD) which may underlie hyposensitivity to both noxious and innocuous stimuli and perhaps also self-injurious behaviour among these individuals. The study contributes novel information on possible mechanisms involved in BPD manifestations.

Efficiency of Tissue Penetration by Currents Induced by 3 Electrotherapeutic Techniques: A Comparative Study Using a Novel Deep-Tissue Measuring Technique.

BACKGROUND: Electrotherapy provides a wide range of treatment alternatives for musculoskeletal pathologies. However, for the electrical stimulation to exert a significant therapeutic effect, the induced current must often penetrate deep inside the target tissue. OBJECTIVE: The objective was to systematically compare the penetration efficiency of 3 electrotherapeutic stimulation modalities: transcutaneous electrical nerve stimulation (TENS), interferential (IF) stimulation, and combined therapy with pulsed ultrasound and IF current (CTPI). DESIGN: This was a comparative, experimental laboratory study. METHODS: The penetration efficiency was evaluated as a voltage difference between 2 of an 8-contact spinal cord stimulation array. Each of 20 participants with a preimplanted spinal cord stimulation array was stimulated with TENS (3 different electrode configurations), IF current (3 configurations), and CTPI (1 configuration). RESULTS: Significant differences in penetration efficiency were found between the various stimulation conditions and electrode configurations. CTPI showed the highest penetration efficiency, followed by IF, and finally TENS. Penetration efficiency was inversely and significantly correlated with skinfold thickness in all conditions, but this correlation was lowest for the CTPI stimulation. LIMITATIONS: Our study design did not include a condition of combined therapy with pulsed ultrasound and TENS, and it did not directly control for current or voltage density under the stimulating electrodes. In addition, further research is required to determine whether a higher stimulation intensity of the target tissue is advantageous clinically. CONCLUSIONS: Pending further testing, CTPI stimulation could prove more effective than IF and TENS in reaching deeper tissues, especially considering the variability in adipose tissue thickness in the population, for example, in cases of patients with obesity.

Personal experience and attitudes of pain medicine specialists in Israel regarding the medical use of cannabis for chronic pain.

INTRODUCTION: The scientific study of the role of cannabis in pain medicine still lags far behind the growing use driven by public approval. Accumulated clinical experience is therefore an important source of knowledge. However, no study to date has targeted physicians who actually use cannabis in their daily practice. METHODS: Registered, active, board-certified pain specialists in Israel (n=79) were asked to complete a Web-based survey. The survey was developed using the Qualtrics Online Survey Software. Questions were formulated as multiple-choice questions, and these addressed three areas of interest: 1) doctors' personal experience; 2) the role of cannabis in pain medicine; and 3) cannabis medicalization and legalization. RESULTS: Sixty-four percent of all practicing pain specialists in Israel responded. Almost all prescribe cannabis. Among them, 63% find cannabis moderately to highly effective, 56% have encountered mild or no side effects, and only 5% perceive it as significantly harmful. Common indications are neuropathic pain (65%), oncological pain (50%), arthralgias (25%), and any intractable pain (29%). Leading contraindications are schizophrenia (76%), pregnancy/breastfeeding (65%), and age <18 years (59%). Only 12% rated cannabis as more hazardous than opiates. On a personal note, 45% prefer cannabis for themselves or a family member. Lastly, 54% would like to see cannabis legalized in Israel. CONCLUSION: In this survey, pain clinicians experienced in prescribing cannabis over prolonged periods view it as an effective and relatively safe treatment for chronic pain, based on their own experience. Their responses suggest a possible change of paradigm from using cannabis as the last resort.

The association between severity of depression and prescription opioid misuse among chronic pain patients with and without anxiety: A cross-sectional study.

BACKGROUND: In light of the increased rates of Prescription Opioid (PO) misuse and associated mortality in several developed countries in recent years, efforts have been made to identify populations who may be at increased risk for misuse of POs. Though the association between depression and PO misuse among pain patients is well documented, little is known regarding the effects of severity of depression on rates of misuse. In this study we explored rates of PO misuse among chronic pain patients screening positive for depression according to level of severity. METHODS: Participants included chronic pain patients receiving POs (N = 554). All participants were screened for depression using the Patient Health Questionnaire (PHQ-9; cut-off scores of 5, 10, 15, and 20 for mild, moderate, moderate-severe and severe depression, respectively) and for opioid misuse using the Current Opioid Misuse Measure (COMM). Logistic regression analyses controlling for additional sociodemographic and clinical factors were conducted. RESULTS: Participants who screened positive for depression were at significantly increased odds to screen positive for opioid misuse (Adjusted Odds Ratio (AOR) = 3.63; 95% Confidence Interval (CI) = 1.71-7.7) compared to those without depression. Severity of depression was significantly associated with increased odds for opioid misuse for moderate (AOR = 3.71; 95% CI = 1.01-13.76), moderate-severe (AOR = 6.28; 95% CI = 1.6-24.57) and severe (AOR = 14.66; 95% CI = 3.28-65.52) depression but not among those who screened positive for mild depression (AOR = 1.49; 95% CI = 0.39-5.68). LIMITATIONS: Cross-sectional study. CONCLUSIONS: Our results highlight the need to properly asses and address level of severity of co-morbid depression among chronic pain patients receiving POs.

Misuse of prescription opioids among chronic pain patients suffering from anxiety: A cross-sectional analysis.

OBJECTIVE: In the past two decades, chronic pain has been increasingly treated with prescription opioids, particularly in developed countries. This has drawn public concern of possible risks associated with the potential misuse of prescriptions opioids. Previous research has indicated that this may be particularly true among individuals suffering from co-occurring psychiatric disorders. The present study sought to explore rates of misuse among chronic pain patients prescribed opioids, comparing individuals with and without anxiety. METHODS: Chronic pain patients receiving prescription opioids (N=554) were screened for anxiety using the Generalized Anxiety Disorder (GAD-7) scale and for opioid misuse using the Current Opioid Misuse Measure (COMM). RESULTS: Among patients who screened positive for anxiety (GAD-7≥10), 50% also screened positive for opioid misuse, compared to 10% among those without anxiety. After controlling for possible confounding sociodemographic and clinical variables, patients with anxiety were significantly more prone to screen positive for opioid misuse (Adjusted Odds Ratio (AOR)=2.18; 95% Confidence Interval (CI)=1.37-4.17) compared to those without anxiety. This was maintained when conducting separate comparisons for severe, but not mild or moderate, level of anxiety. CONCLUSIONS: These findings highlight the importance of detecting and addressing co-occurring anxiety when treating patients with chronic pain who receive prescription opioids.

Depression and anxiety among chronic pain patients receiving prescription opioids and medical marijuana.

BACKGROUND: High rates of depression and anxiety have been consistently reported among patients suffering from chronic pain. Prescription opioids are one of the most common modalities for pharmacological treatment of pain, however in recent years medical marijuana(MM) has been increasingly used for pain control in the US and in several countries worldwide. The aim of this study was to compare levels of depression and anxiety among pain patients receiving prescription opioids and MM. METHODS: Participants were patients suffering from chronic pain treated with prescription opioids (OP,N=474), MM (N=329) or both (OPMM,N=77). Depression and anxiety were assessed using the depression module of the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder scale (GAD-7). RESULTS: Prevalence of depression among patients in the OP, MM and OPMM groups was 57.1%, 22.3% and 51.4%, respectively and rates of anxiety were 48.4%, 21.5% and 38.7%, respectively. After controlling for confounders, patients in the OP group were significantly more likely to screen positive for depression (Adjusted Odds Ratio(AOR)=6.18;95%CI=4.12-9.338) and anxiety(AOR=4.12;CI=3.84-5.71)) compared to those in the MM group. Individuals in the OPMM group were more prone for depression (AOR for depression=3.34;CI=1.52-7.34)) compared to those in the MM group. LIMITATIONS: Cross-sectional study, restricting inference of causality. CONCLUSIONS: Levels of depression and anxiety are higher among chronic pain patients receiving prescription opioids compared to those receiving MM. Findings should be taken into consideration when deciding on the most appropriate treatment modality for chronic pain, particularly among those at risk for depression and anxiety.

Magnetic resonance-guided focused ultrasound treatment of facet joint pain: summary of preclinical phase.

STUDY DESIGN: A phantom experiment, two thermocouple experiments, three in vivo pig experiments, and a simulated treatment on a healthy human volunteer were conducted to test the feasibility, safety, and efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) for treating facet joint pain. OBJECTIVE: The goal of the current study was to develop a novel method for accurate and safe noninvasive facet joint ablation using MRgFUS. SUMMARY OF BACKGROUND DATA: Facet joints are a common source of chronic back pain. Direct facet joint interventions include medial branch nerve ablation and intra-articular injections, which are widely used, but limited in the short and long term. MRgFUS is a breakthrough technology that enables accurate delivery of high-intensity focused ultrasound energy to create a localized temperature rise for tissue ablation, using MR guidance for treatment planning and real-time feedback. METHODS: We validated the feasibility, safety, and efficacy of MRgFUS for facet joint ablation using the ExAblate 2000® System (InSightec Ltd., Tirat Carmel, Israel) and confirmed the system's ability to ablate the edge of the facet joint and all terminal nerves innervating the joint. A phantom experiment, two thermocouple experiments, three in vivo pig experiments, and a simulated treatment on a healthy human volunteer were conducted. RESULTS: The experiments showed that targeting the facet joint with energies of 150-450 J provides controlled and accurate heating at the facet joint edge without penetration to the vertebral body, spinal canal, or root foramina. Treating with reduced diameter of the acoustic beam is recommended since a narrower beam improves access to the targeted areas. CONCLUSIONS: MRgFUS can safely and effectively target and ablate the facet joint. These results are highly significant, given that this is the first study to demonstrate the potential of MRgFUS to treat facet joint pain.

Prevalence of fibromyalgia syndrome in patients referred to a tertiary pain clinic.

BACKGROUND: Fibromyalgia syndrome (FMS), the prototypical central pain augmentation syndrome, is characterized by widespread pain and tenderness. Although patients referred to tertiary care pain clinics are recognized as suffering from chronic pain, they are generally considered to have pain attributable to discrete peripheral, nociceptive, or neuropathic etiology.The purpose of the current study was to assess the prevalence of FMS among consecutive patients referred to a tertiary pain clinic and to evaluate the contribution of central pain to the clinical impact upon such patients. METHODS: Eighty-five consecutive patients (38 were male, and 47 were female) attending a pain clinic were assessed for the presence of FMS. The presence of FMS was determined according to the 1990 American College of Rheumatology (ACR) classification criteria. Quality of life and physical functioning were assessed, utilizing a structured questionnaire. RESULTS: The ACR criteria for the classification of FMS were fulfilled by 41.2% of patients. Patients fulfilling FMS criteria ranked significantly lower on all domains of the SF-36, including general health, physical functioning, role limitation due to physical and emotional problems, vitality, social functioning, bodily pain, and mental health. Composite physical and mental health scores were significantly lower among patients fulfilling ACR FMS criteria. Patients fulfilling the ACR criteria for FMS felt significantly more tenderness, based on the mean number of tender points and the mean tenderness threshold, when compared with patients not fulfilling the ACR FMS criteria. CONCLUSIONS: A significant proportion of patients referred to a tertiary pain clinic were found to fulfill the ACR criteria for classification of FMS and thus exhibit an important element of central pain. Central pain augmentation should be actively searched for and therapeutically addressed in the evaluation and management of all patients with chronic pain.

Topical ophthalmic amethocaine alleviates trigeminal neuralgia pain.

BACKGROUND: Trigeminal neuralgia (TGN) is a challenging pain syndrome. AIM: To test the effectiveness of local instillation of ophthalmic solution of amethocaine in relieving the pain of TGN. METHODS: We performed an open-label prospective study in 40 consecutive currently treated patients suffering from TGN with a reported visual analog scale (VAS) >8 (severe pain). The patients received two drops of amethocaine 1% instilled on the cornea ipsilateral to the painful side. Pain score assessment using VAS was recorded pre- and post-treatment. RESULTS: A total of 32 (80%) patients reported a significant reduction in pain 10 minutes after drops instillation as compared with pre-treatment pain score. Pre-treatment VAS score was 8.53 ± 0.6 as compared with 4.78 ± 1.83 post-amethocaine treatments (P < 0.00001). CONCLUSION: Topical ophthalmic instillation of amethocaine 1% can be considered as an immediate effective method for pain paroxysm of TGN.

Terminating migraine with allodynia and ongoing central sensitization using parenteral administration of COX1/COX2 inhibitors.

OBJECTIVE: To determine whether delayed infusion of COX1/COX2 inhibitors (ketorolac, indomethacin) will stop migraine in allodynic patients, and suppress ongoing sensitization in central trigeminovascular neurons in the rat. BACKGROUND: The majority of migraineurs seeking secondary or tertiary medical care develop cutaneous allodynia during the course of migraine, a sensory abnormality mediated by sensitization of central trigeminovascular neurons in the spinal trigeminal nucleus. Triptan therapy can render allodynic migraineurs pain free within a narrow window of time (20 to 120 minutes) that opens with the onset of pain and closes with the establishment of central sensitization. Can drugs that tackle ongoing central sensitization render allodynic migraineurs pain free after the window for triptan therapy has expired? METHODS: Patients exhibiting migraine with allodynia were divided in two groups (n=14, each): group 1 received delayed sumatriptan injection (6 mg) 4 hours after onset of attack--which failed to render them pain free-and ketorolac infusion (two 15-mg boluses) 2 hours later; group 2 received delayed ketorolac monotherapy 4 hours after onset of attack. Pain intensity (visual analog scale) and skin sensitivity (quantitative sensory testing) were measured when the patients were migraine free (baseline); 4 hours after onset of migraine (just before treatment); 2 hours after sumatriptan; 1 hour after ketorolac. In the rat, we tested whether infusion of ketorolac (0.4 mg/kg) or indomethacin (1 mg/kg) will block ongoing sensitization in peripheral and central trigeminovascular neurons. The induction of sensitization (using topical application of inflammatory soup on the dura) and its suppression by COX1/COX2 inhibitors were assessed by monitoring changes in spontaneous activity and responses to mechanical and thermal stimuli. RESULTS: Patients had normal skin sensitivity in the absence of migraine, and presented cutaneous allodynia 4 hours after onset of migraine. In group 1, all patients continued to exhibit allodynia 2 hours after sumatriptan treatment, and none of them became pain free. However, 71% and 64% of the patients in groups 1 and 2, respectively, were rendered free of pain and allodynia within 60 minutes of ketorolac infusion. Nonresponders from both groups, in contrast to the responders, had had a history of opioid treatment. In the rat, infusion of COX1/COX2 inhibitors blocked sensitization in meningeal nociceptors and suppressed ongoing sensitization in spinal trigeminovascular neurons. This inhibitory action was reflected by normalization of neuronal firing rate and attenuation of neuronal responsiveness to mechanical stimulation of the dura, as well as mechanical and thermal stimulation of the skin. CONCLUSIONS: The termination of migraine with ongoing allodynia using COX1/COX2 inhibitors is achieved through the suppression of central sensitization. Although parenteral administration of COX1/COX2 inhibitors is impractical as routine migraine therapy, it should be the rescue therapy of choice for patients seeking emergency care for migraine. These patients should never be treated with opioids, particularly if they had no prior opioid exposure.