Pharmacological Treatment of Pain in Osteoarthritis: A Descriptive Review.

PURPOSE OF REVIEW: Osteoarthritis (OA) is the most common form of arthritis that is characterized by loss of articular cartilage and new formation of bone. Pain and functional disability are common features that lead to disability and poor quality of life. This review discusses the current state of knowledge concerning the treatment of pain in OA, with a focus on pharmacological treatments. This includes the use of non-steroidal anti-inflammatory drugs, acetaminophen, and other disease-modifying agents. RECENT FINDINGS: An updated review of the role of anti-nerve growth factor monoclonal antibodies and other novel agents in the treatment of OA is also presented. In addition, a discussion of current research on biological agents such as small molecules targeting ion channels and G protein-coupled receptors is included. These new pharmacological interventions expand the frontier for treatment of patients with OA. The purpose of the review is to provide clinicians with information about the effectiveness of different pharmacological modalities in order to enable them to make the best choices for the treatment of their patients.

Trigeminal Neuralgia: A Clinical Review for the General Physician.

General practitioners (GPs) are often the first clinicians to encounter patients with trigeminal neuralgia (TN). Given the gravity of the debilitating pain associated with TN, it is important for these clinicians to learn how to accurately diagnose and manage this illness. The objective of this article is to provide an up-to-date literature review regarding the presentation, classification, diagnosis, and the treatment of TN. This article also focuses on the long-term management of these patients under the care of GPs. GPs play an important role in the management of patients with TN by following the evidence-based management guidelines. The most important aspects of the management of TN are discussed in this review article.

Cranial Neuralgias.

Advances in diagnostic modalities have improved the understanding of the pathophysiology of neuropathic pain involving head and face. Recent updates in nomenclature of cranial neuralgias and facial pain have rationalized accurate diagnosis. Clear diagnosis and localization of pain generators are paramount, leading to better use of medical and targeted surgical treatments.

Detailed analysis of allergic cutaneous reactions to spinal cord stimulator devices.

The use of spinal cord stimulation (SCS) devices to treat chronic, refractory neuropathic pain continues to expand in application. While device-related complications have been well described, inflammatory reactions to the components of these devices remain underreported. In contrast, hypersensitivity reactions associated with other implanted therapies, such as endovascular and cardiac rhythm devices, have been detailed. The purpose of this case series is to describe the clinical presentation and course of inflammatory reactions as well as the histology of these reactions. All patients required removal of the entire device after developing inflammatory reactions over a time course of 1-3 months. Two patients developed a foreign body reaction in the lead insertion wound as well as at the implantable pulse generator site, with histology positive for giant cells. One patient developed an inflammatory dermatitis on the flank and abdomen that resolved with topical hydrocortisone. "In vivo" testing with a lead extension fragment placed in the buttock resulted in a negative reaction followed by successful reimplantation of an SCS device. Inflammatory reactions to SCS devices can manifest as contact dermatitis, granuloma formation, or foreign body reactions with giant cell formation. Tissue diagnosis is essential, and is helpful to differentiate an inflammatory reaction from infection. The role of skin patch testing for 96 hours may not be suited to detect inflammatory giant cell reactions that manifest several weeks post implantation.

Loin pain hematuria syndrome-visceral or neuropathic pain syndrome?

Loin pain hematuria syndrome (LPHS) is a rare pain syndrome, which is somewhat poorly characterized and challenging to treat. The condition of LPHS is still controversial and there is no consensus of validated diagnostic criteria or optimal treatment strategies. The epidemiology of LPHS is unknown and the mechanisms/etiologies contributing to LPHS remain uncertain. There exists some debate whether LPHS represents neuropathic pain or visceral pain. Curiously, for such a controversial pain syndrome there is substantially more written in the literature regarding surgical-type treatments than conservative treatments. A brief review of LPHS potential pathophysiology and potential treatment approaches is presented.

Retrospective review of the efficacy and safety of repeated pulsed and continuous radiofrequency lesioning of the dorsal root ganglion/segmental nerve for lumbar radicular pain.

BACKGROUND: Chronic lumbosacral radicular pain is a common source of radiating leg pain seen in pain management patients. These patients are frequently managed conservatively with multiple modalities including medications, physical therapy, and epidural steroid injections. Radiofrequency has been used to treat chronic radicular pain for over 30 years; however, there is a paucity of literature about the safety and efficacy of repeat radiofrequency lesioning. OBJECTIVES: To determine the safety, success rate, and duration of pain relief of repeat pulsed radiofrequency (PRF) and continuous radiofrequency (CRF) lesioning of the dorsal root ganglion (DRG)/ sacral segmental nerves (SN) in patients with chronic lumbosacral radicular pain. STUDY DESIGN: Retrospective chart review SETTING: Outpatient multidisciplinary pain center METHODS: Medical record review of patients who were treated with pulsed and continuous radiofrequency lesioning of the lumbar dorsal root ganglia and segmental nerves and who reported initial success were evaluated for recurrence of pain and repeat radiofrequency treatment. Responses to subsequent treatments were compared to initial treatments for success rates, average duration of relief, and adverse neurologic side-effects. LIMITATIONS: Retrospective chart review without a control group. RESULTS: Twenty-six women and 24 men were identified who received 50% pain relief or better after PRF and CRF of the lumbar DRG/ sacral SN for lumbosacral radicular pain. The mean age was 62 years (range, 25-86). The mean duration of relief for the 40 patients who had 2 treatments was 4.7 months (range 0-24; Se [standard error] 0.74). Twenty-eight patients had 3 treatments with an average duration of relief of 4.5 months (range 0-19 months; Se 0.74). Twenty patients had 4 treatments with a mean duration of relief of 4.4 months (range 0.5-18; Se 0.95) and 18 patients who had 5 or more treatments received an average duration of relief of 4.3 months (range 0.5-18; Se 1.03). The average duration of relief and success frequency remained constant after each subsequent radiofrequency treatment. Of the 50 total patients, there was only 1 reported complication, specifically, transient thigh numbness which resolved after one week. CONCLUSIONS: Repeated pulsed and continuous radiofrequency ablation of the lumbar dorsal root ganglion/segmental nerve shows promise to be a safe and effective long-term palliative management for lumbosacral radicular pain in some patients.

Lack of association between migraine headache and patent foramen ovale: results of a case-control study.

BACKGROUND: Clinical observations of migraine headache symptoms in patients with a patent foramen ovale (PFO), both of which conditions are highly prevalent, have raised the question of a possible pathophysiological relationship. We sought to evaluate the assumption of an association between migraine headaches and the presence of PFO by use of a large case-control study. METHODS AND RESULTS: We conducted a case-control study to assess the prevalence of PFO in subjects with and without migraine. Case subjects were those with a history of migraine (diagnosed by neurologists at a specialty academic headache clinic). Control subjects were healthy volunteers without migraine 1:1 matched on the basis of age and sex with case subjects. Presence of PFO was determined by transthoracic echocardiogram with second harmonic imaging and transcranial Doppler ultrasonography during a standardized procedure of infused agitated saline contrast with or without Valsalva maneuver and a review of the results by experts blinded to case-control status. PFO was considered present if both studies were positive. Odds ratios were calculated with conditional logistic regression in the matched cohort (n=288). In the matched analysis, the prevalence of PFO was similar in case and control subjects (26.4% versus 25.7%; odds ratio 1.04, 95% confidence interval 0.62 to 1.74, P=0.90). There was no difference in PFO prevalence in those with migraine with aura and those without (26.8% versus 26.1%; odds ratio 1.03, 95% confidence interval 0.48 to 2.21, P=0.93). CONCLUSIONS: We found no association between migraine headaches and the presence of PFO in this large case-control study.

Incidence and root cause analysis of wrong-site pain management procedures: a multicenter study.

BACKGROUND: Medical errors exact an inordinate toll on healthcare costs. One of the most publicized and analyzed type of medical error is wrong-site surgery. Yet, despite the burgeoning number of procedures performed, no literature exists on wrong-site pain management injections. The purpose of this study was to estimate the relative incidence and determine the causes of wrong-site pain management procedures. METHODS: Quality improvement records were examined during a 2-yr period from four civilian academic teaching hospitals, three military treatment facilities, and three private practices, for "sentinel" events involving wrong-site pain management procedures. A total of 13 cases (incidence 0.027%; 95% CI 0.01-0.05%) were identified from approximately 48,941 collective procedures of which 52.4% were deemed to be "at risk" for the occurrence. Root cause analyses were then conducted to determine the origin of each error. RESULTS: The 13 cases included five wrong-side transforaminal epidural steroid injections, six other wrong-side injections, and two wrong-level minimally invasive surgical procedures. In only one case was the "universal protocol" completely followed, and in nine procedures, multiple lapses occurred in protocol. Three patients had bilateral pathology, and in seven cases, the patient knew at the time that the wrong side was being injected. In no instance did any technical, legal, or professional consequences ensue from the error. CONCLUSIONS: Wrong-site nerve blocks occur more frequently in pain management centers than has previously been acknowledged. Adaptation of the universal protocol to nerve blocks and strict adherence to widely accepted guidelines may prevent wrong-site interventional pain procedures.

Low and therapeutic doses of antidepressants are associated with similar response in the context of multimodal treatment of pain.

BACKGROUND: Antidepressants are prescribed in a wide range of doses to treat both depression and chronic pain, with optimal psychopharmacology individualized for each patient. In the past decade more antidepressants from different chemical classes have become available and are being used for the treatment of both chronic pain and depression. OBJECTIVE: To review the utilization pattern changes and compare response rates of different classes and doses of antidepressants for various pain conditions in the context of multimodal therapies. DESIGN: Chart review. METHODS: We reviewed 5,916 records at an outpatient multidisciplinary pain center. Of these, 379 records were for patients diagnosed with cancer pain. Because the mechanisms and treatment approaches to cancer pain can differ greatly from non-cancer chronic pain, these records were excluded from the analysis. We assessed 1,506 medical records for patients with chronic non-caner pain who had used at least one antidepressant, with the main outcome measure being the Numeric Rating Pain Scale, 0-10. RESULTS: Of the 5,916 charts reviewed, 1,506 (25.4%) chronic non-cancer pain charts recorded the prescription of at least one antidepressant. Most patients received a combination of medications and procedures. Of the 450 patients receiving secondary amines, favorable responses were recorded for 340 (76%) patients, while 103 (23%) did not respond and 7 had unknown responses. Of the 492 patients receiving tertiary amines, favorable responses were recorded for 375 (76%) patients, while 113 (23%) did not respond, and 4 had unknown responses. Of the 533 patients receiving SSRI/SNRIs, favorable responses were recorded for 382 (72%) patients, while 147 (28%) did not respond, and 4 had unknown responses. Of the 369 patients receiving atypical antidepressants, favorable responses were recorded for 272 (74%) patients, while 94 (25%) did not respond, and 3 had unknown responses. LIMITATIONS: A retrospective study design and the use of antidepressants as a part of multimodal treatment of pain. CONCLUSION: The data suggest that in the context of multimodal treatment for chronic pain, antidepressant therapy at both low and therapeutic doses demonstrates similar response rates. Tricyclic antidepressants (TCAs), which include secondary and tertiary amines, as well as SSRI/SNRIs and atypicals, all appear to show similar favorable response rates.

The use of opioids in the treatment of osteoarthritis: when, why, and how?

As life expectancy increases every decade, the incidence and prevalence of osteoarthritis (OA) also will increase. Despite progress in our knowledge of the pathophysiology of OA, the management of OA-mediated pain continues to challenge physicians. Concern regarding the cardiovascular effects of cyclooxygenase-2 inhibitors and the gastrointestinal and renal side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) in general has limited the use of these medications in the management of chronic non-cancer pain. Appropriately dosed and monitored use of opioids for OA pain, when more conservative methods have failed, has potentially fewer life-threatening complications associated with it than the more commonly and often less successfully employed pharmacotherapeutic approaches to care. When used as part of a multimodal approach to pain control, opioids are a safe and effective treatment for joint pain, including that of OA. Patients for whom NSAIDs are contraindicated, or for whom combined acetaminophen, tramadol, and NSAID therapy is ineffective, may be started on low-dose opioids and titrated as needed and tolerated. Patient education and informed consent, exercise, complementary medicine, and the use of a controlled substance agreement increases the likelihood of patient compliance with treatment guidelines, improving functional capacity and quality of life.

A retrospective review of clinical presentation, thyroid autoimmunity, laboratory characteristics, and therapies used in patients with chronic idiopathic urticaria.

BACKGROUND: Our knowledge of autoimmune characteristics of chronic idiopathic urticaria (CIU) is limited. OBJECTIVE: To study the demographic, laboratory, and clinical patterns of a cohort of patients with CIU. METHODS: We evaluated 236 patients with CIU seen in a recent 2-year span. For serum basophil activation testing (BAT-CD203), the samples were sent to the National Jewish Medical and Research Center for donor basophil CD203 expression assay (5% cell surface expression was considered a positive result). RESULTS: Of the 236 patients with CIU, 77% were females with a mean age of 39 years. The mean age of males was 43 years. Of patients tested for BAT-CD203 (50 females and 8 males), 38% of females (n = 19) and 13% of males (n = 1) had positive test results. Of the 146 females and 42 males tested for thyroid autoimmunity (TA), 34% of females (n = 50) and 17% of males (n = 7) had underlying TA. Nine BAT-CD203-positive females (47%) had TA compared with 11 of 30 BAT-CD203-negative females (37%). No correlation was found between antinuclear antibodies and BAT-CD203. Cyclosporine or corticosteroids were used in 28% of the study population, with another 16% requiring a trial of additional third-line agents with or without prednisone/cyclosporine. There was no significant difference in the maximum number of medications used in subgroups based on the presence or absence of BAT-CD203 and TA. CONCLUSIONS: The frequency of TA in patients with CIU was 30%, which is higher than that previously reported. The frequency of TA and BAT-CD203 positivity was higher in females. In this clinical cohort, there was no correlation between BAT-CD203 and TA.

What is mechanical back pain and how best to treat it?

Back pain is one of the most common patient complaints brought forth to physicians. Mechanical back pain accounts for 97% of cases, arising from spinal structures such as bone, ligaments, discs, joints, nerves, and meninges. Acute back pain in the absence of progressive neurologic deficits and other underlying nonmechanical causes may be treated conservatively, with specific emphasis on maintaining activity levels and function. Mechanical back pain persisting for more than 4 to 6 weeks may warrant further diagnostic testing and imaging. Common causes of mechanical back pain include spinal stenosis, herniated discs, zygapophysial joint pain, discogenic pain, vertebral fractures, sacroiliac joint pain, and myofascial pain. A wide variety of treatments are available, with different treatments specifically targeted toward different causes. A balanced approach, which takes into account patient psychosocial factors and incorporates multidisciplinary care, increases the likelihood of success from back pain interventions.

Vertebral osteomyelitis: a potentially catastrophic outcome after lumbar epidural steroid injection.

BACKGROUND AND OBJECTIVE: Epidural steroid injections are commonly used to palliate the symptoms of spinal stenosis. Deep tissue infection is a known potential complication of these injections. There have been no previous published cases of osteomyelitis without epidural abscess after such injections. We present a case in an elderly patient who presented only with persistent axial low back pain following a lumbar epidural steroid injection (LESI). We emphasize early patient evaluation, consideration of infectious predisposing factors, sterile technique, and skin disinfectant. DESIGN: Open-label case report. CASE DESCRIPTION: A 77-year-old diabetic male with a history of radicular pain related to lumbar spinal stenosis was treated successfully several years prior with a series of lumbar epidural steroid injections (LESI) and was re-treated with LESIs for recurrent symptoms. Following his second epidural injection, he presented with back pain and induration at the injection site without fever or neurological deficits. Urgent magnetic resonance imaging (MRI) revealed a soft tissue abscess extending close to the epidural space around the corresponding L4/L5 vertebral level. The patient recovered after incision and drainage of the abscess which was associated with an osteomyelitis of the L4 and L5 vertebral spine. The causative organism was methicillin-resistant Staphylococcus Aureus. CONCLUSION: This case demonstrates that even with proper aseptic techniques, immune-compromised patients who are colonized with an aggressive micro-organism may develop a potentially catastrophic infectious complication if subtle persistent symptomatic complaints are not promptly and carefully evaluated.

The role of extraocular and facial muscle trigger points in cephalalgia.

Trigger points play a part in the development and maintenance of chronic headache states. This article reviews the physiology of trigger points, with a focus on the -latest understanding of their biochemistry. The importance of facial muscle and extraocular muscle trigger points is only beginning to be understood; the data exploring their role in headache are reviewed. The concept of central sensitization and the way in which it relates to trigger points and headache is explained, along with treatment strategies for helping patients with their pain.

Response to pulsed and continuous radiofrequency lesioning of the dorsal root ganglion and segmental nerves in patients with chronic lumbar radicular pain.

OBJECTIVES: We aimed to prospectively evaluate the response and safety of pulsed and continuous radiofrequecy lesioning of the dorsal root ganglion/segmental nerves in patients with chronic lumbosacral radicular pain. METHODS: Seventy-six patients with chronic lumbosacral radicular pain refractory to conventional therapy met the inclusion criteria and were randomly assigned to one of 2 types of treatment, pulsed radiofrequency lesioning of the dorsal root ganglion/segmental nerve or pulsed radiofrequency followed immediately by continuous radiofrequency. Patients were carefully evaluated for neurologic deficits and side effects. The response was evaluated at 2 months and was then tracked monthly. A Kaplan-Meier analysis was used to illustrate the probability of success over time and a Box-Whisker analysis was applied to determine the mean duration of a successful analgesic effect. RESULTS: Two months after undergoing radiofrequency treatment, 70% of the patients treated with pulsed radiofrequency and 82% treated with pulsed and continuous radiofrequency had a successful reduction in pain intensity. The average duration of successful analgesic response was 3.18 months (+/- 2.81) in the group treated with pulsed radiofrequency and 4.39 months (+/-3.50) in those patients treated with pulsed and continuous radiofrequency lesioning. A Kaplan-Meier analysis illustrated that in both treatment groups the chance of success approached 50% in each group at 3 months. The vast majority of patients had lost any beneficial effects by 8 months. There was no statistical difference between the 2 treatment groups. No side effects or neurological deficits were found in either group. CONCLUSION: Pulsed mode radiofrequency of the dorsal root ganglion of segmental nerves appears to be a safe treatment for chronic lumbosacral radicular pain. A significant number of patients can derive at least a short-term benefit. The addition of heat via continuous radiofrequency does not offer a significant advantage. A randomized controlled trial is now required to determine the effectiveness of pulsed radiofrequency.

Factors predicting success and failure for cervical facet radiofrequency denervation: a multi-center analysis.

BACKGROUND AND OBJECTIVES: The concept of radiofrequency denervation has recently come under question in light of several studies showing minimal to no benefit. One possibility proposed for these negative outcomes is poor selection criteria. Unlike virtually all other spine interventions, the factors associated with success and failure for cervical facet denervation have yet to be determined. The purpose of this study is to determine which demographic, clinical and treatment factors are associated with cervical facet radiofrequency denervation outcomes. METHODS: Data were garnered from 3 academic medical centers on 92 patients with chronic neck pain who underwent radiofrequency denervation after a positive response to diagnostic local anesthetic blocks. Success was defined as at least 50% pain relief lasting at least 6 months. Variables evaluated for their association with outcome included age, sex, duration of pain, opioid use, pain referral pattern, paraspinal tenderness, pain exacerbated by extension/rotation, magnetic resonance image abnormalities, diabetes, smoking, scoliosis, obesity, prior surgery, and levels treated. RESULTS: The only clinical variable associated with success was paraspinal tenderness. Factors associated with treatment failure included radiation to the head, opioid use, and pain exacerbated by neck extension and/or rotation. CONCLUSIONS: Selecting patients based on key clinical variables may increase the chance of treatment success for cervical facet radiofrequency denervation.

Exploding vs. imploding headache in migraine prophylaxis with Botulinum Toxin A.

Migraine headache is routinely managed using medications that abort attacks as they occur. An alternative approach to migraine management is based on prophylactic medications that reduce attack frequency. One approach has been based on local intramuscular injections of Botulinum Toxin Type A (BTX-A). Here, we explored for neurological markers that might distinguish migraine patients who benefit from BTX-A treatment (100 units divided into 21 injections sites across pericranial and neck muscles). Responders and non-responders to BTX-A treatment were compared prospectively (n=27) and retrospectively (n=36) for a host of neurological symptoms associated with their migraine. Data pooled from all 63 patients are summarized below. The number of migraine days per month dropped from 16.0+/-1.7 before BTX-A to 0.8+/-0.3 after BTX-A (down 95.3+/-1.0%) in 39 responders, and remained unchanged (11.3+/-1.9 vs. 11.7+/-1.8) in 24 non-responders. The prevalence of aura, photophobia, phonophobia, osmophobia, nausea, and throbbing was similar between responders and non-responders. However, the two groups offered different accounts of their pain. Among non-responders, 92% described a buildup of pressure inside their head (exploding headache). Among responders, 74% perceived their head to be crushed, clamped or stubbed by external forces (imploding headache), and 13% attested to an eye-popping pain (ocular headache). The finding that exploding headache was impervious to extracranial BTX-A injections is consistent with the prevailing view that migraine pain is mediated by intracranial innervation. The amenability of imploding and ocular headaches to BTX-A treatment suggests that these types of migraine pain involve extracranial innervation as well.

The use of opioids in the treatment of osteoarthritis: when, why, and how?

As life expectancy increases every decade, the incidence and prevalence of osteoarthritis (OA) also will increase. Despite progress in our knowledge of the pathophysiology of OA, the management of OA-mediated pain continues to challenge physicians. Concern regarding the cardiovascular effects of cyclooxygenase-2 inhibitors and the gastrointestinal and renal side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) in general has limited the use of these medications in the management of chronic non-cancer pain. Appropriately dosed and monitored use of opioids for OA pain, when more conservative methods have failed, has potentially fewer life-threatening complications associated with it than the more commonly and often less successfully employed pharmacotherapeutic approaches to care. When used as part of a multimodal approach to pain control, opioids are a safe and effective treatment for joint pain, including that of OA. Patients for whom NSAIDs are contraindicated, or for whom combined acetaminophen, tramadol, and NSAID therapy is ineffective, may be started on low-dose opioids and titrated as needed and tolerated. Patient education and informed consent, exercise, complementary medicine, and the use of a controlled substance agreement increases the likelihood of patient compliance with treatment guidelines, improving functional capacity and quality of life.

Fundamentals of interventional pain medicine.

Chronic pain is one of the most common and challenging medical problems facing our society. The specialty of pain medicine has grown steadily in recent years, largely because of the recognition that multiple factors contribute to chronic pain. The practice of pain medicine is multidisciplinary in approach, incorporating modalities from various specialties to ensure the comprehensive evaluation and treatment of the pain patient. The integration of various specialties such as anesthesiology, neurology, neurologic surgery, orthopedic surgery, physical medicine, and psychiatry is essential to treating patients with chronic pain and to establishing continuity of care. Research in the last 30 years has developed a variety of alternatives or adjuncts to opiates for chronic pain, including neuroactive medications, counterstimulation methods, and cognitive-behavioral therapies. Pain medicine specialists have provided leadership in the development of the practice, with the application of a wide verity of central and peripheral nerve blocks, sympathetic and neurolytic blocks, intradiscal procedures, neuromodulation techniques, intrathecal infusion systems, and other technical procedures that are firmly linked to a biomedical model of pain.