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.

tDCS-induced analgesia and electrical fields in pain-related neural networks in chronic migraine.

OBJECTIVE: We investigated in a sham-controlled trial the analgesic effects of a 4-week treatment of transcranial direct current stimulation (tDCS) over the primary motor cortex in chronic migraine. In addition, using a high-resolution tDCS computational model, we analyzed the current flow (electric field) through brain regions associated with pain perception and modulation. METHODS: Thirteen patients with chronic migraine were randomized to receive 10 sessions of active or sham tDCS for 20 minutes with 2 mA over 4 weeks. Data were collected during baseline, treatment and follow-up. For the tDCS computational analysis, we adapted a high-resolution individualized model incorporating accurate segmentation of cortical and subcortical structures of interest. RESULTS: There was a significant interaction term (time vs group) for the main outcome (pain intensity) and for the length of migraine episodes (ANOVA, P < .05 for both analyses). Post-hoc analysis showed a significant improvement in the follow-up period for the active tDCS group only. Our computational modeling studies predicted electric current flow in multiple cortical and subcortical regions associated with migraine pathophysiology. Significant electric fields were generated, not only in targeted cortical regions but also in the insula, cingulate cortex, thalamus, and brainstem regions. CONCLUSIONS: Our findings give preliminary evidence that patients with chronic migraine have a positive, but delayed, response to anodal tDCS of the primary motor cortex. These effects may be related to electrical currents induced in pain-related cortical and subcortical regions.

The Burden of Metastatic Cancer-Induced Bone Pain: A Narrative Review.

Bone pain is one of the most common forms of pain reported by cancer patients with metastatic disease. We conducted a review of oncology literature to further understand the epidemiology of and treatment approaches for metastatic cancer-induced bone pain and the effect of treatment of painful bone metastases on the patient's quality of life. Two-thirds of patients with advanced, metastatic, or terminal cancer worldwide experience pain. Cancer pain due to bone metastases is the most common form of pain in patients with advanced disease and has been shown to significantly reduce patients' quality of life. Treatment options for cancer pain due to bone metastases include nonsteroidal anti-inflammatory drugs, palliative radiation, bisphosphonates, denosumab, and opioids. Therapies including palliative radiation and opioids have strong evidence supporting their efficacy treating cancer pain due to bone metastases; other therapies, like bisphosphonates and denosumab, do not. There is sufficient evidence that patients who experience pain relief after radiation therapy have improved quality of life; however, a substantial proportion are nonresponders. For those still requiring pain management, even with available analgesics, many patients are undertreated for cancer pain due to bone metastases, indicating an unmet need. The studies in this review were not designed to determine why cancer pain due to bone metastases was undertreated. Studies specifically addressing cancer pain due to bone metastases, rather than general cancer pain, are limited. Additional research is needed to determine patient preferences and physician attitudes regarding choice of analgesic for moderate to severe cancer pain due to bone metastases.

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.

Thalamic sensitization transforms localized pain into widespread allodynia.

OBJECTIVE: Focal somatic pain can evolve into widespread hypersensitivity to nonpainful and painful skin stimuli (allodynia and hyperalgesia, respectively). We hypothesized that transformation of headache into whole-body allodynia/hyperalgesia during a migraine attack is mediated by sensitization of thalamic neurons that process converging sensory impulses from the cranial meninges and extracephalic skin. METHODS: Extracephalic allodynia was assessed using single unit recording of thalamic trigeminovascular neurons in rats and contrast analysis of blood oxygenation level-dependent (BOLD) signals registered in functional magnetic resonance imaging (fMRI) scans of patients exhibiting extracephalic allodynia. RESULTS: Sensory neurons in the rat posterior thalamus that were activated and sensitized by chemical stimulation of the cranial dura exhibited long-lasting hyperexcitability to innocuous (brush, pressure) and noxious (pinch, heat) stimulation of the paws. Innocuous, extracephalic skin stimuli that did not produce neuronal firing at baseline (eg, brush) became as effective as noxious stimuli (eg, pinch) in eliciting large bouts of neuronal firing after sensitization was established. In migraine patients, fMRI assessment of BOLD signals showed that brush and heat stimulation at the skin of the dorsum of the hand produced larger BOLD responses in the posterior thalamus of subjects undergoing a migraine attack with extracephalic allodynia than the corresponding responses registered when the same patients were free of migraine and allodynia. INTERPRETATION: We propose that the spreading of multimodal allodynia and hyperalgesia beyond the locus of migraine headache is mediated by sensitized thalamic neurons that process nociceptive information from the cranial meninges together with sensory information from the skin of the scalp, face, body, and limbs.

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.

Implanted auriculotemporal nerve stimulator for the treatment of refractory chronic migraine.

OBJECTIVE: To report a case of improved pain control and function in a patient with chronic migraine after treatment with auriculotemporal nerve stimulation. METHODS: The patient is a 52-year-old woman with refractory pain in the bilateral temporal distribution and marked phonophobia as a result of chronic migraine. RESULTS: After a successful trial period, the patient underwent implantation of bilateral peripheral nerve stimulators targeting the auriculotemporal nerves. At 16 months of follow up, her average pain intensity declined from 8-9/10 on the numeric rating scale to 5/10. Her function improved as assessed by the Migraine Disability Assessment, from total disability (grade IV) to mild disability (grade II). Her phonophobia became far less debilitating. CONCLUSION: Auriculotemporal nerve stimulation may be useful tool in the treatment of refractory pain in the temporal distribution due to chronic migraine.

A fMRI evaluation of lamotrigine for the treatment of trigeminal neuropathic pain: pilot study.

Using functional magnetic resonance imaging (fMRI) methods, we evaluated the effects of lamotrigine vs placebo in a double-blind 1:1 randomized trial. Six patients with neuropathic pain were recruited for the study. All subjects had baseline pain >4/10 on a visual analog scale (VAS) and allodynia to brush as inclusion criteria for the study. Patients underwent two fMRI sessions, with half of the subjects receiving placebo first and half receiving drug first (based on the blinding protocol). Lamotrigine decreased their average pain intensity level from 5.6 to 3.5 on a VAS. All subjects had brush, cold, and heat applied to the affected and mirror-unaffected sides of their face. The results show: 1) in a small cohort, lamotrigine had a significant effect on heat VAS but not on the other stimuli; and 2) contrast analysis of fMRI results for heat stimuli applied to the affected face for lamotrigine vs placebo produced an overall decrease in blood oxygen dependent level signal, suggesting a potential inhibitory effect of the drug on predominantly cortical regions (frontal, parietal, and temporal).

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.

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.

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.

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.

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.

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.

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.

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.

Immune responses to Campylobacter and serum autoantibodies in patients with complex regional pain syndrome.

We hypothesised that some complex regional pain syndromes (CRPS) may have a postinfectious and/or autoimmune basis. Sera from 92 patients with CRPS and 92 controls were investigated for immunoreactivity to Campylobacter strains and to rodent tissues. Both IgA-antibodies to Campylobacter and tissue-specific reactivity were often present in patients with short disease duration (< or = 1.5 years). Patients with minimal preceding trauma had stronger nervous tissue-specific reactivity than other patients, regardless of disease duration. These results provide preliminary evidence for immune activation early in CRPS and, additionally, that patients with minimal trauma may comprise an autoimmune subgroup.

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.

Subjective nature of lower limb radicular pain.

BACKGROUND: Lumbar pathologies may cause the perception of leg pain, but the character of this pain has not been described. Diagnosis is often based on dermatomal charts, but observations reveal that the pain is not typically perceived on the skin. OBJECTIVE: To document the incidence of superficial versus deep pain localization among patients with lumbar radicular pain. METHODS: Twenty-five patients with lower limb radicular pain were questioned to determine the specific localization of their pain. The investigator categorized the pain location into general areas (eg, posterior thigh or anterior leg). Patients were asked if their pain was perceived as being on the skin or deep, as a forced choice question. These data were gathered in 2 conditions: at rest (spontaneous pain) and during a straight leg raise test (mechanically evoked pain). Data were recorded using a standardized form for later analysis. RESULTS: In all cases, symptoms were reported to be in deep structures. Pain was typically reported at sites correlated with multiple spinal levels. CONCLUSION: Because radicular pain symptoms are perceived in deep structures rather than on the skin, the diagnostic value of dermatomal charts is questioned. Clinicians are advised to be specific when questioning patients with radicular pain symptoms and to refer to myotomal and sclerotomal charts when making diagnoses.

Radiofrequency lesioning of the L2 ramus communicans in managing discogenic low back pain.

BACKGROUND: Discogenic low back pain is a common cause of chronic low back pain that remains a treatment challenge. The innervation and transmission of nociceptive information from painful lumbar discs has only recently been better described. OBJECTIVE: To report initial experience of effectiveness of radiofrequency lesioning of L2 ramus communicans in managing discogenic pain. STUDY DESIGN: A prospective, case series. METHODS: A case series of 5 patients who had radiofrequency lesioning of the ramus communicans at the L2 level. All patients had discogenic low back pain and had diagnostic blocks with local anesthetic at the level of the L2 ramus communicans demonstrating significant pain relief. Continuous radiofrequency lesioning at 80 degrees C of the L2 ramus communicans for 60 seconds was performed. Standard outcome measures of reduction in the visual analogue scale (VAS), improvement in function, reduction in pain medication, and consistent improvement in low back pain with repeating of the procedure after its initial effect has worn off were recorded. RESULTS: All five patients had consistent pain relief after a minimum of 2 radiofrequency lesioning treatments approximately 4 months apart. Four of the five patients had a reduction in pain medication, and all reported improvement in sitting tolerance and functioning. There were no side effects or complications. CONCLUSION: Radiofrequency lesioning of the L2 ramus communicans seems to offer partial relief for patients suffering from discogenic pain. Further studies are needed to confirm our results.