Number Of Pain Conditions Research Articles

Increasing risk of cannabis use disorder among U.S. veterans with chronic pain: 2005-2019.

In the United States, cannabis is increasingly used to manage chronic pain. Veterans Health Administration (VHA) patients are disproportionately affected by pain and may use cannabis for symptom management. Because cannabis use increases the risk of cannabis use disorders (CUDs), we examined time trends in CUD among VHA patients with and without chronic pain, and whether these trends differed by age. From VHA electronic health records from 2005 to 2019 (∼4.3-5.6 million patients yearly), we extracted diagnoses of CUD and chronic pain conditions ( International Classification of Diseases [ ICD ]- 9-CM , 2005-2014; ICD-10-CM , 2016-2019). Differential trends in CUD prevalence overall and age-stratified (<35, 35-64, or ≥65) were assessed by any chronic pain and number of pain conditions (0, 1, or ≥2). From 2005 to 2014, the prevalence of CUD among patients with any chronic pain increased significantly more (1.11%-2.56%) than those without pain (0.70%-1.26%). Cannabis use disorder prevalence increased significantly more among patients with chronic pain across all age groups and was highest among those with ≥2 pain conditions. From 2016 to 2019, CUD prevalence among patients age ≥65 with chronic pain increased significantly more (0.63%-1.01%) than those without chronic pain (0.28%-0.47%) and was highest among those with ≥2 pain conditions. Over time, CUD prevalence has increased more among VHA patients with chronic pain than other VHA patients, with the highest increase among those age ≥65. Clinicians should monitor symptoms of CUD among VHA patients and others with chronic pain who use cannabis, and consider noncannabis therapies, particularly because the effectiveness of cannabis for chronic pain management remains inconclusive.

Spinal TRPA1 Contributes to the Mechanical Hypersensitivity Effect Induced by Netrin-1.

Netrin-1, a chemoattractant expressed by floor plate cells, and one of its receptors (deleted in colorectal cancer) has been associated with pronociceptive actions in a number of pain conditions. Here, we addressed the question of whether spinal TRPC4/C5 or TRPA1 are among the downstream receptors contributing to pronociceptive actions induced by netrin-1. The experiments were performed on rats using a chronic intrathecal catheter for administration of netrin-1 and antagonists of TRPC4/C5 or TRPA1. Pain sensitivity was assessed behaviorally by using mechanical and heat stimuli. Effect on the discharge rate of rostral ventromedial medullary (RVM) pain control neurons was studied in lightly anesthetized animals. Netrin-1, in a dose-related fashion, induced mechanical hypersensitivity that lasted up to three weeks. Netrin-1 had no effect on heat nociception. Mechanical hypersensitivity induced by netrin-1 was attenuated by TRPA1 antagonist Chembridge-5861528 and by the control analgesic compound pregabalin both during the early (first two days) and late (third week) phase of hypersensitivity. TRPC4/C5 antagonist ML-204 had a weak antihypersensitivity effect that was only in the early phase, whereas TRPC4/C5 antagonist HC-070 had no effect on hypersensitivity induced by netrin-1. The discharge rate in pronociceptive ON-like RVM neurons was increased by netrin-1 during the late but not acute phase, whereas netrin-1 had no effect on the discharge rate of antinociceptive RVM OFF-like neurons. The results suggest that spinal TRPA1 receptors and pronociceptive RVM ON-like neurons are involved in the maintenance of submodality-selective pronociceptive actions induced by netrin-1 in the spinal cord.

Musculoskeletal orofacial pains - overlap between tension type headache and temporomandibular disorder

A number of pain conditions in the head share clinical presentations such as being dull, diffuse, pressing, bilateral and longer-lasting with moderate intensity, often with pain referrals to the neck-shoulder regions, higher prevalence in women before menopause, aggravated by oral functions and stress and associated with considerable psycho-social distress and reduced quality of life. The International Classification of Headache Disorders (ICHD) have well-established criteria for tension-type headache and Headaches attributed to Temporomandbular Disorders (HA-TMD). The Diagnostic Criteria for TMD has set the standards for operationalized, reliable and valid diagnosis of myalgia and myofascial pain related to the jaw muscles and a variant of the HA-TMD diagnosis. Recently also International Classification for Orofacial Pain (ICOP) has proposed subtyping of the muscle pain conditions based on temporal characteristics: acute, infrequent, frequent and chronic occurrence. Nevertheless, the overarching question should be to what extent may underlying pathophysiology vary between these entities and what would the therapeutic implications be? The talk will attempt to review the musculoskeletal orofacial pain conditions, present new findings about the potential overlap and further phenotyping, and critically discuss the clinical ramifications.

Stressors and Pain Over the Late-Life Course: Findings from Two Parent Longitudinal Studies of Aging and Health

With this study we sought to determine how older adults’ stressors influence their levels and rates of change in pain during the late-life span. We harmonized repeated measures data from two parent longitudinal studies of aging and health, Longitudinal Late-Life Health (LLLH; n=1,1884) and the Health and Retirement Study (HRS; n=7,703), to determine how participants’ stressor levels in the domains of finances, spouse, children, extended family, and friends, and in stressors overall, influenced their average levels and rates of change in painful conditions, pain severity, and pain interference over 13-year (LLLH) and 8-year (HRS) intervals. Participants’ within-person stressor levels declined somewhat, whereas their number of painful conditions, pain severity, pain interference, and prescription painkiller use increased steadily, over these intervals. In both the LLLH and HRS samples, participants who experienced higher average stressor levels over the 13- and 8-year intervals had more numerous painful conditions and higher pain severity over these intervals. In the HRS sample, they also experienced higher levels of pain interference. These effects occurred independent of the demographic characteristics of age, gender, and race. In general, participants’ stressor levels did not influence rates of increase in their pain. Gender and race had some moderating effects on associations between stressors and pain, but these occurred only within certain specific stressor and pain domains. These findings demonstrate an association between stressors and pain across the late-life course. Further research is needed to determine the mediating mechanisms that account for this association and the moderating factors that affect its strength.

Virtual reality as a non-pharmacologic analgesic for fasciotomy wound infections in acute compartment syndrome: a case report

BackgroundFasciotomy is a life-saving procedure to treat acute compartment syndrome, a surgical emergency. As fasciotomy dramatically improves wound pain, it should be performed as soon as possible. Moreover, delays in the use of fasciotomy can increase the rate of wound infections. Once the fasciotomy wound is infected, pain control is achieved via the long-term use of opioids or anti-inflammatory analgesics. However, the administration of high doses of opioids may cause complications, such as respiratory depression, over-sedation, and constipation. Therefore, treatment methods other than narcotic administration should be established to better manage the pain caused by fasciotomy wound infections.Virtual reality has recently been introduced in analgesic therapy as a replacement, or complement, to conventional pharmacological treatments. Its use has been extensively studied in the pain management of patients with burns. An increasing number of painful conditions are being successfully treated with virtual reality. Here, we report a case of acute compartment syndrome complicated by fasciotomy wound infection.Case presentationA 40-year-old Japanese man suffering from acute compartment syndrome of his leg due to a car accident trauma was treated with a fasciotomy to decompress intra-compartmental pressure and restore tissue perfusion, and admitted to an intensive care unit. Unfortunately, as the open fasciotomy wound was complicated by infection, he complained of hyperalgesia and severe pain during wound debridement. He was therefore given acetaminophen and high-dose intravenous patient-controlled analgesic fentanyl (35 μg/kg per day) to reduce the pain. Despite these efforts, the pain was poorly controlled and opioid-induced side effects such as respiratory depression were observed. An immersive virtual reality analgesic therapy aimed at distraction and relaxation was used and effectively alleviated the pain. Three sessions of virtual reality analgesic therapy over 2 days produced sustainable analgesic effects, which led to a 25–75% dose reduction in fentanyl administration and the concomitant alleviation of respiratory depression.ConclusionsThis case suggests the feasibility of virtual reality analgesic therapy for pain management of fasciotomy wound complications in acute compartment syndromes. Virtual reality represents a treatment option that would reduce analgesic consumption and eliminate opioid-induced respiratory depression to treat fasciotomy wound infection.

Impaired intrinsic functional connectivity between the thalamus and visual cortex in migraine without aura

BackgroundResting-state functional magnetic resonance imaging (fMRI) has confirmed disrupted visual network connectivity in migraine without aura (MwoA). The thalamus plays a pivotal role in a number of pain conditions, including migraine. However, the significance of altered thalamo-visual functional connectivity (FC) in migraine remains unknown. The goal of this study was to explore thalamo-visual FC integrity in patients with MwoA and investigate its clinical significance.MethodsResting-state fMRI data were acquired from 33 patients with MwoA and 22 well-matched healthy controls. After identifying the visual network by independent component analysis, we compared neural activation in the visual network and thalamo-visual FC and assessed whether these changes were linked to clinical characteristics. We used voxel-based morphometry to determine whether functional differences were dependent on structural differences.ResultsThe visual network exhibited significant differences in regions (bilateral cunei, right lingual gyrus and left calcarine sulcus) by inter-group comparison. The patients with MwoA showed significantly increased FC between the left thalami and bilateral cunei and between the right thalamus and the contralateral calcarine sulcus and right cuneus. Furthermore, the neural activation of the left calcarine sulcus was positively correlated with visual analogue scale scores (r = 0.319, p = 0.043), and enhanced FC between the left thalamus and right cuneus in migraine patients was negatively correlated with Generalized Anxiety Disorder scores (r = − 0.617, p = 0.005).ConclusionOur data suggest that migraine distress is exacerbated by aberrant feedback projections to the visual network, playing a crucial role in migraine physiological mechanisms. The current study provides further insights into the complex scenario of migraine mechanisms.

Employment status, hours working, and gainful earnings after spinal cord injury: relationship with pain, prescription medications for pain, and nonprescription opioid use.

Cross-sectional self-report assessment. Econometric modeling. Identify the relationship of multiple pain indicators, prescription pain medication, nonprescription opioid use, and multiple indicators of quality employment among those with spinal cord injury (SCI). Data were collected at a medical university in the Southeastern United States (US). Participants included 4670 adults with traumatic SCI of at least one-year duration who were enrolled in a study of health and longevity. They were identified from three sources including a specialty hospital and two population-based state SCI surveillance systems. Econometric modeling was used for three outcome variables: employment status, hours per week spent working, and earnings. Several pain parameters were significantly related to multiple employment outcomes. Prescription medication to treat pain was associated with lower odds of employment, fewer hours working, and lower conditional earnings. Nonprescription opioid use was only related to fewer hours working. Painful days, number of painful conditions, and pain intensity were all related to employment outcomes, but the pattern varied by outcome. The number of painful conditions was most consistently related to employment. Multiple demographic, injury, and educational factors were related to employment, with better outcomes among those with less severe SCI and greater educational achievements. The presence of significant pain and use of either prescription pain medications or the use of nonprescription opioids may have a significant adverse effect on both the probability of employment and quality of employment. Rehabilitation and vocational professionals should routinely assess pain and associated medications in vocational and career planning.

Dysfunctional Coping Mechanisms Contribute to Dry Eye Symptoms.

Dysfunctional coping behaviors, such as catastrophizing, have been implicated in pain severity and chronicity across several pain disorders. However, the impact of dysfunctional coping has not been examined under the context of dry eye (DE). This study evaluates relationships between catastrophizing and measures of DE, including pain severity and pain-related daily interference. The population consisted of patients seen at Miami Veterans Affairs eye clinic between April 2016 and October 2017. Patients filled out standardized questionnaires assessing symptoms of DE and eye pain, non-ocular pain, mental health, coping behaviors (Pain Catastrophizing Scale, PCS), and pain-related daily interference as a perceived impact on quality of life (Multidimensional Pain Inventory, Interference Subscale, MPI-Interference), and all patients underwent an ocular surface examination. In total, 194 patients participated, with a mean age of 58.8 ± 9.6 years, the majority being male, non-Hispanic, and black. PCS (catastrophizing) was correlated with DE symptom severity, including Dry-Eye Questionnaire 5 (DEQ5; r = 0.41, p < 0.0005), Ocular Surface Disease Index (OSDI; r = 0.40, p < 0.0005), and neuropathic-like eye pain (Neuropathic Pain Symptom Inventory-Eye (NPSI-Eye; r = 0.48, p < 0.0005). Most tear metrics, on the other hand, did not correlate with PCS. Linear regressions showed that PCS, non-ocular pain intensity, and number of pain conditions were significant predictors of DEQ5 (overall DE symptoms), while PCS and non-ocular pain intensity were predictors of NPSI-Eye scores, as were insomnia scores and analgesic use. In a separate analysis, PCS and DE symptoms (OSDI) associated with pain-related interference (MPI-Interference) along with non-ocular pain intensity, post-traumatic stress disorder (PTSD), number of pain conditions, and non-Hispanic ethnicity. These findings suggest that catastrophizing is not significantly related to signs of DE, but is strongly associated to pain-related symptoms of DE and daily interference due to pain.

TRPA1: a molecular view.

The transient receptor potential ankyrin 1 (TRPA1) ion channel is expressed in pain-sensing neurons and other tissues and has become a major target in the development of novel pharmaceuticals. A remarkable feature of the channel is its long list of activators, many of which we are exposed to in daily life. Many of these agonists induce pain and inflammation, making TRPA1 a major target for anti-inflammatory and analgesic therapies. Studies in human patients and in experimental animals have confirmed an important role for TRPA1 in a number of pain conditions. Over the recent years, much progress has been made in elucidating the molecular structure of TRPA1 and in discovering binding sites and modulatory sites of the channel. Because the list of published mutations and important molecular sites is steadily growing and because it has become difficult to see the forest for the trees, this review aims at summarizing the current knowledge about TRPA1, with a special focus on the molecular structure and the known binding or gating sites of the channel.

Spinal PKC activation — Induced neuronal HMGB1 translocation contributes to hyperalgesia in a bone cancer pain model in rats

Bone cancer pain (BCP) remains a serious complication of malignancy, which is an intractable clinical problem due to the gap in knowledge of its underlying mechanisms. Recent studies have demonstrated that the major involvement of neuroinflammation, particularly high-mobility group box 1 (HMGB1), which was identified as a late mediator of inflammation, in a number of pain conditions. However, the underlying mechanisms and functions of HMGB1 release in spinal cord, and its contributions to the development of BCP as well, are poorly understood. In the present study, we examined the theory that PKC activation lead to nuclear translocation and cytosolic HMGB1 secretion, which subsequently induces spinal neuro inflammatory responses (cytokine release) causing hyperalgesia. Our results showed that PKC activation and HMGB1 release in spinal neurons as well as mechanical allodynia in BCP rats, were all attenuated by intrathecal administration of the PKC inhibitor Gö6983 and aggravated by its activator PMA. Intrathecal administration of anti-HMGB1 antibody also alleviated hypersensitivity caused by BCP. Meanwhile, phospho-PKC and cellular HMGB1 were found co-localized in neurons, but not in microglia and astrocytes, of the spinal dorsal horns of tumor-bearing rats. Additionally, we found that HMGB1 translocation from nuclei to cytoplasm may be the consequence of PKC translocation into the nuclei, which occurred 9 days after tumor inoculation. Total p-HMGB1 as well as nuclear and cytoplasmic HMGB1 expression levels were tested in response to broad-spectrum PKC inhibitor Gö6983 or activator PMA in BCP rats. Together, these findings suggest that bone cancer related hyperalgesia is driven by PKC induced phosphorylation of HMGB1, which results in its translocation from the nucleus, and releasing from the cytosol of the dorsal horn, and the activation of spinal pro-inflammatory mediators.

Neighborhood Socioeconomic Status and Receipt of Opioid Medication for New Back Pain Diagnosis.

Although treatment for new back pain is heavily guideline driven, deviations occur frequently. Neighborhood socioeconomic status (nSES) may contribute to these deviations. Determine whether nSES is associated with type of treatment provided for patients seeking treatment for new back pain in primary care clinics. This retrospective cohort was conducted in academic internal and family medicine practices. Data were examined from the Primary Care Patient Data Registry. Eligibility criteria included age ≥18 years, free of HIV and cancer, and presenting to primary care with a new diagnosis of back pain, resulting in1646 patients included. Patients' nSES was determined using ZIP code and calculating a validated index of 7 census-tract variables. Multinomial logistic regression was used to measure the association between nSES and 3 treatment outcomes compared with no pharmacologic management. Outcomes included opioid prescription, nonsteroidal anti-inflammatory (NSAID)/muscle relaxant prescription, or combined opioid/nonopioid treatment within 90 days of initial presentation. Covariates included age, sex, race, high clinic utilization (HCU), depression, anxiety, substance use, obesity, comorbidities, smoking, number of pain conditions, and physical therapy (PT) referral. The cohort was 67.9% female with an average age of 55.72 years (Standard Error [SE] = 0.387). Compared with no pharmacologic treatment, individuals in the low nSES group had 63% higher odds of receiving an opioid only compared with the high nSES group (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.01 to 2.62). There was no significant association between nSES and odds of nonopioid or combined treatment compared with no pharmacotherapy (OR, 1.17; 95% CI, 0.97 to 1.50), (OR, 1.09; 95% CI, 0.67 to 1.78), respectively. Covariates associated with increased odds of opioid only included HCU, ever smoker, and increasing comorbidity index. PT referral was associated with NSAID/muscle relaxant only, and increasing age and comorbidity index were inversely associated with odds of NSAID/muscle relaxant only. Finally, covariates associated with increased odds of receiving both therapies included high clinic utilizusation, ever smoking, and PT referral. These data characterize a possible association between low nSES and increased risk of receiving an opioid only when being treated for new back pain. This may be evidence that patients of low nSES are at increased risk of receiving guideline-noncompliant treatment for new back pain.

17β-Estradiol Enhances ASIC Activity in Primary Sensory Neurons to Produce Sex Difference in Acidosis-Induced Nociception

Sex differences have been reported in a number of pain conditions. Women are more sensitive to most types of painful stimuli than men, and estrogen plays a key role in the sex differences in pain perception. However, it is unclear whether there is a sex difference in acidosis-evoked pain. We report here that both male and female rats exhibit nociceptive behaviors in response to acetic acid, with females being more sensitive than males. Local application of exogenous 17β-estradiol (E2) exacerbated acidosis-evoked nociceptive response in male rats. E2 and estrogen receptor (ER)-α agonist 1,3,5-Tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole, but not ERβ agonist 2,3-bis(4-hydroxyphenyl)-propionitrile, replacement also reversed attenuation of the acetic acid-induced nociceptive response in ovariectomized females. Moreover, E2 can exert a rapid potentiating effect on the functional activity of acid-sensing ion channels (ASICs), which mediated the acidosis-induced events. E2 dose dependently increased the amplitude of ASIC currents with a 42.8 ± 1.6 nM of EC50. E2 shifted the concentration-response curve for proton upward with a 50.1% ± 6.2% increase of the maximal current response to proton. E2 potentiated ASIC currents via an ERα and ERK1/2 signaling pathway. E2 also altered acidosis-evoked membrane excitability of dorsal root ganglia neurons and caused a significant increase in the amplitude of the depolarization and the number of spikes induced by acidic stimuli. E2 potentiation of the functional activity of ASICs revealed a peripheral mechanism underlying this sex difference in acetic acid-induced nociception.

Disrupted default mode network connectivity in migraine without aura

BackgroundResting-state functional magnetic resonance imaging (RS-fMRI) has demonstrated disrupted default mode network (DMN) connectivity in a number of pain conditions, including migraine. However, the significance of altered resting-state brain functional connectivity in migraine is still unknown. The present study is aimed to explore DMN functional connectivity in patients with migraine without aura (MwoA) and investigate its clinical significance.MethodsTo calculate and compare the resting-state functional connectivity of the DMN in 20 patients with MwoA, during the interictal period, and 20 gender- and age-matched HC, Brain Voyager QX was used. Voxel-based morphometry was used to assess whether between-group differences in DMN functional connectivity were related to structural differences. Secondary analyses explored associations between DMN functional connectivity, clinical and neuropsychological features of migraineurs.ResultsIn comparison to HC, patients with MwoA showed decreased connectivity in prefrontal and temporal regions of the DMN. Functional abnormalities were unrelated to detectable structural abnormalities or clinical and neuropsychological features of migraineurs.ConclusionsOur study provides further evidence of disrupted DMN connectivity in patients with MwoA. We hypothesize that a DMN dysfunction may be related to behavioural processes such as a maladaptive response to stress which seems to characterize patients with migraine.

Mechanisms of Pain Modulation by Sex Hormones in Migraine

A number of pain conditions, acute as well as chronic, are much more prevalent in women, such as temporomandibular disorder (TMD), irritable bowel syndrome, fibromyalgia, and migraine. The association of female sex steroids with these nociceptive conditions is well known, but the mechanisms of their effects on pain signaling are yet to be deciphered. We reviewed the mechanisms through which female sex steroids might influence the trigeminal nociceptive pathways with a focus on migraine. Sex steroid receptors are located in trigeminal circuits, providing the molecular substrate for direct effects. In addition to classical genomic effects, sex steroids exert rapid nongenomic actions to modulate nociceptive signaling. Although there are only a handful of studies that have directly addressed the effect of sex hormones in animal models of migraine, the putative mechanisms can be extrapolated from observations in animal models of other trigeminal pain disorders, like TMD. Sex hormones may regulate sensitization of trigeminal neurons by modulating expression of nociceptive mediator such as calcitonin gene-related peptide. Its expression is mostly positively regulated by estrogen, although a few studies also report an inverse relationship. Serotonin (5-Hydroxytryptamine [5-HT]) is a neurotransmitter implicated in migraine; its synthesis is enhanced in most parts of brain by estrogen, which increases expression of the rate-limiting enzyme tryptophan hydroxylase and decreases expression of the serotonin re-uptake transporter. Downstream signaling, including extracellular signal-regulated kinase activation, calcium-dependent mechanisms, and cAMP response element-binding activation, are thought to be the major signaling events affected by sex hormones. These findings need to be confirmed in migraine-specific animal models that may also provide clues to additional ion channels, neuropeptides, and intracellular signaling cascades that contribute to the increased prevalence of migraine in women.

Sentralnervesystemets mekanismer for smertehemming

Several endogenous factors regulate the perception of pain. Understanding of pain-alleviating mechanisms is increasing, which is useful both for doctors who treat pain-ridden patients and for researchers interested in the physiology of pain. This article provides an overview of such mechanisms. This review article is based on literature identified through a non-systematic search in PubMed. Endogenous pain-alleviating mechanisms are mainly controlled by different parts of the reticular substance, and are normally activated by painful stimulation. Expectation of pain reduction (placebo analgesic effect), painful stimulation in other sites and high blood pressure are examples of factors which may increase the body's endogenous pain-alleviating mechanisms. Opioid-sensitive cells in the brain stem are important for endogenous pain alleviation. Reduced endogenous pain alleviation is found in a number of painful conditions, but it has not been clarified whether reduced endogenous pain inhibition is a cause of or a result of chronic pain. Strengthening of the body's own mechanisms for pain alleviation is possible and potentially useful in treatment of pain-ridden patients.

Allodynia in Migraine: Association With Comorbid Pain Conditions

Cutaneous allodynia (CA) in migraine is a clinical manifestation of central nervous system sensitization. Several chronic pain syndromes and mood disorders are comorbid with migraine. In this study we examine the relationship of migraine-associated CA with these comorbid conditions. We also evaluate the association of CA with factors such as demographic profiles, migraine characteristics, and smoking status that may have an influence on the relationships of CA to pain and mood. Data are from a cross-sectional multicenter study of comorbid conditions in persons seeking treatment in headache clinics. Diagnosis of migraine was determined by a physician based on the International Classification of Headache Disorders-II criteria. Participants completed a self-administered questionnaire ascertaining sociodemographics, migraine-associated allodynia, physician-diagnosed comorbid medical and psychiatric disorders, headache-related disability, current depression, and anxiety. A total of 1413 migraineurs (mean age = 42 years, 89% women) from 11 different headache treatment centers completed a survey on the prevalence of comorbid conditions. Aura was reported by 38% and chronic headache by 35% of the participants. Sixty percent of the study population reported at least one migraine-related allodynic symptom, 10% reported > or =4 symptoms. Symptoms of CA were associated with female gender, body mass index, current smoking, presence of aura, chronic headaches, transformed headaches, severe headache-related disability, and duration of migraine illness from onset. The prevalence of self-reported physician diagnosis of comorbid pain conditions (irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia) and psychiatric conditions (current depression and anxiety) was also associated with symptoms of CA. Adjusted ordinal regression indicated a significant association between number of pain conditions and severity of CA (based on symptom count). Adjusting for sociodemographics, migraine characteristics, and current depression and anxiety, the likelihood of reporting symptoms of severe allodynia was much higher in those with 3 or more pain conditions (odds ratio = 3.03, 95% confidence interval: 1.78-5.17), and 2 pain conditions (odds ratio = 2.67, 95% confidence interval: 1.78-4.01) when compared with those with no comorbid pain condition. Symptoms of CA in migraine were associated with current anxiety, depression, and several chronic pain conditions. A graded relationship was observed between number of allodynic symptoms and the number of pain conditions, even after adjusting for confounding factors. This study also presents the novel association of CA symptoms with younger age of migraine onset, and with cigarette smoking, in addition to confirming several previously reported findings.

Rofecoxib: clinical pharmacology and clinical experience

Background: Rofecoxib is a member of a subgroup of nonsteroidal anti-inflammatory drugs (NSAIDs) known as cyclooxygenase-2 (COX-2)—selective inhibitors. It has been studied in adult and elderly patients in a number of painful conditions (primary dysmenorrhea, acute pain after dental and orthopedic surgery, osteoarthritis [OA], and rheumatoid arthritis). Objective: This review discusses the clinical pharmacology of and clinical experience with rofecoxib, and the role of COX-2—selective inhibitors in clinical practice. Methods: Pertinent studies were identified through searches of MEDLINE and EMBASE, as well as the Web sites and proceedings of relevant scientific meetings. Results: Although the published literature is limited, the data indicate that rofecoxib is an effective analgesic agent for the painful conditions in which it has been studied. As a COX-2—selective inhibitor, rofecoxib offers safety advantages over traditional NSAIDs. In clinical trials, gastrointestinal (GI) toxicity, including mucosal damage, perforation, ulcers, and bleeding, occurred significantly less often in healthy volunteers and patients treated with rofecoxib than in those who received NSAIDs such as ibuprofen, naproxen, or diclofenac (all comparisons, P < 0.001). In terms of renal toxicity, rofecoxib does not appear to offer a safety advantage over traditional NSAIDs. Rofecoxib has not been shown to affect platelets (bleeding time and platelet aggregation), unlike traditional NSAIDs. Conclusions: Rofecoxib is an appropriate choice for patients who do not obtain adequate analgesia with acetaminophen and those who have not obtained adequate analgesia from, cannot tolerate, or are at risk for GI toxicity with traditional NSAIDs. Patients who require chronic analgesic medication (ie, those with OA), including those who take other medications daily for comorbid conditions, may also benefit from the once-daily dosing regimen of rofecoxib.

A possible role for saliva as a diagnostic fluid in patients with chronic pain

Objectives: The focus of this review was on proteins and peptides found in saliva. Of greatest interest were those neuropeptides relevant to nociception and to the pathogenesis of chronic pain syndromes. An additional goal was to develop a standardized protocol to collect saliva for laboratory assessment. Methods: Data were obtained through discussion with experts at the medical schools in San Antonio and Heidelberg and a Medline literature search involving all relevant studies from 1966 to 1997. The literature search was based on the following key terms: saliva, serotonin, neuropeptide, substance P (SP), calcitonin gene-related peptide (CGRP), and nerve growth factor (NGF). Results: The mean concentration of SP in the saliva of healthy normal controls ranged from 9.6 to 220 pg/mL. Generally, the concentration of SP was approximately three times higher in saliva than in plasma. In a number of painful conditions, particularly tension headache, substantial elevations of salivary SP were found. Mean values for salivary CGRP in healthy controls were approximately 22 pmol/L and were significantly elevated in patients with migraine attacks or cluster headache. There were no data to indicate prior quantitative determination of NGF in human saliva. Conclusions: After sampling and processing techniques have been standardized,measurement of neuropeptides in human saliva could provide a valuable tool for the study of patients with chronic painful disorders such as rheumatoid arthritis, osteoarthritis, and even fibromyalgia syndrome.