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Renew Your Subscription and List Your Practice for Free!Chronic pain sufferers are using our pain specialist directory to find pain specialists in your area. This technique uses local anesthetic blocks in conjunction with electric cell signaling treatment (EST) to successfully treat neuropathies of all causes.By Robert H. A neuropathy occurs as a result of basic pathologic processes gone awrya€”either from injury or disease.
It is compelling to note that the course of DPN, as well as other neuropathies, generally is progressive. Although our clinics have not yet initialized formal double-blinded control studies, our clinical outcomes strongly suggest that the CET protocol is making a substantive difference in patientsa€™ lives and certainly warrants more detailed consideration. Four primary nerve fibers are important in small fiber (sensory) neuropathy: A-delta, afferent C, efferent C, and A-beta. Unlike muscles, which use either oxygen or glucose metabolic pathways, nerve cells are limited to the oxidative reductive metabolic system, or Krebs cycle.10,11 The Krebs cycle requires an immediate defense response to assure neural integrity and survival during a hypo-oxidative state.
As the synaptic junctions between the axons of one nerve cell and the dendrites of the next nerve widen, normal signal transmission can become compromised. Conductivity relies on minerals and specific neurotransmitters in the synaptic fluid to enable propagation of the nerve signal.
The initial sensory perception associated with atrophying nerves and enlarged synaptic clefts often is reported by the patient as tingling or electric sensation.
Ephatic cross firing co-existing with numbness may also explain why patients can have pain, dysesthesia, and numbness at the same locations at the same time. The sensory function of afferent A-delta and C fiber is best measured by the A-delta nerve conduction study (NCS), thermal evoked potentials, and functional magnetic resonance imaging (fMRI).
These efferent fibers control the tone of local arterioles, and, critically, contribute to the pathophysiology of small vascular structures and small nerve fibers (which are viable only as a function of these tiny arterioles). Tests of functional improvement are generally considered more robust than anatomic testing.
Despite the many described causes of peripheral neuropathy, the pathophysiology of simultaneous and synergistic decrease in vascular and neuronal function remains constant throughout the process and creates a pathological cascade.
Do you recommend using technology (smartphone apps, Fitbits, etc) to help your patients become more active? Vertical Health Media, LLC does not, by publication of the advertisements contained herein, express endorsement or verify the accuracy and effectiveness of the products and claims contained therein. Practical Pain Management is sent without charge 10 times per year to pain management clinicians in the US.
New insights into genetic backgrounds of rheumatoid arthritis patients may help guide treatment decisions. Like cancer, RA is a progressive disease, one in which genetics have influence, and now, researchers are taking a cue from cancer treatment approaches.
A recent study assessed hundreds of patients with RA to see how the HS1,2A enhancer polymorphism affected disease activity and response to TNFi therapy. Three-hundred and twenty-nine patients took part in the research, all of which were in the earliest phases of their rheumatoid arthritis (ERA).
Researchers also wanted to assess whether the HS1,2A polymorphism could be related to a different NF-kB pathway activation on B cells.
They found specific genes functionally related to the polymorphism a€“ or a€?focus genesa€? a€“ which appeared to map to 3 networks related to cell death and survival, immunological disease, and cell-to-cell signaling and interaction, the authors reported. Incorporating more precision-based strategies into the RA treatment setting is not a far-fetched idea, according to researchers, especially given the fact gene expression biomarkers already have been used to great success in guiding optimized treatment strategies in the cancer field. Other research also presented at this yeara€™s EULAR meeting suggests blood-based genetic testing could be useful tool for analyzing treatment response to pharmacological treatment, specifically TNFia€™s. Gene level paired-analysis indicated significant changes for patients who responded well to adalimumab, where a downregulation of 1776 transcripts and upregulation of 943 transcripts occurred after 3 months of treatment.
These findings will require validation in a large independent cohort of patients on adalimumab therapy, and since the changes were apparent at 3 months, the biomarkers would not be used as predictive markers before treatment, Mr. Further pathway analysis of the genes revealed a€?both differentially expressed and differentially spliced genetic variants in (good-responding patients) were heavily enriched for relevant processes including antigen processing and presentation, ribosome biogenesis and T- and B-cell receptor signaling.a€? The genes most upregulated were oftentimes encoders for immunoglobulin and MHC II components, perhaps a signal of immune cells migrating from the synovium into the blood, the researchers concluded. Studies reported on in this article were presented as part of this yeara€™s meeting of the European League Against Rheumatism (EULAR). Pain is arguably the most common condition seen in primary care, and the most costly one as well.
A research study at a large HMO studied the costs of chronic pain and other common chronic conditions. Despite the high costs noted in Table 1, pain can usually be treated easily and inexpensively. The subacute phase of pain, from one to six months post-injury, is the period during which transition from acute to chronic pain is most often observed. New guidelines shed light on treatment for this common, autoimmune rheumatic disease.By Matthew J. PMR is a chronic, but treatable, inflammatory syndrome that affects patients aged 50 years or older. Editor’s Note: The authors’ have also written an overview of diagnosis and treatment of polymyalgia rheumatic for your patients. Pulsed radiofrequency energy (PRFE) has multiple medical applications including pain modulation, wound healing, and bone repair.1,2 PRFE refers to a noninvasive, nonthermal method of delivering nonionizing electromagnetic energy to a targeted area with a frequency ranging from 1 to 1000 Hz. The pulsatile delivery, with bursts lasting from 10 Aµsec to 1 msec, allows for dissipation of heat making this method non-ablative.
Mechanisms for proposed analgesia include modulating calcium and calmodulin pathways,5 increasing endogenous opioid precursor mRNA,6 altering transcription of cytokine and matrix metalloprotease levels,7 increasing chondrocyte proliferation,8 and enhancing noradrenergic and serotonergic descending inhibitory pain pathways.9 However the exact mechanism is still not completely understood at this time. The role and effectiveness of PRFE in treating various chronic pain conditions is still being defined, and it is unclear if certain conditions fail to respond. The objective of this observational series was to record the effects and duration of PRFE treatment across various pain syndromes. Eligible patients were required to demonstrate chronic pain unrelieved by a recent procedure or injection.
Patients prescribed PRFE were first offered an outpatient initial trial of transcutaneous PRFE. After receiving the trial, patients were then instructed to take the PRFE device home to use twice daily for 30 minutes. The reviewer collected each subjecta€™s medical diagnosis as determined by radiographs, laboratory results, and clinical judgment. Due to the low sample sizes, statistical significance of the diagnoses was not reported to prevent false comparisons. This series of articles will review current concepts in the compassionate and multidisciplinary treatment of cancer-related paina€”with this article providing a practical guide to pharmaceutical management. Many national and international cancer care organizations have endorsed the use of opioids for the appropriate treatment of cancer-related nociceptive and neuropathic pain of peripheral origin.5 The success of treatment relies on adequate communication of the intensity and character (including persistent and breakthrough characteristics) of the patienta€™s pain, as well as realistic treatment expectations and goals, with treatment agreements and informed consent. However, there continues to be a global lack of training in pain management for providers, resulting in the educational focus on diseases rather than symptoms. The good news is that there is widespread acceptance by pain specialists that opioids are efficacious and should be the mainstay of treatment, particularly for malignant pain.6 Regulatory and law enforcement organizations have recognized that appropriate opioid prescribing is part of the "standard of care" in appropriate patients, and under treating this pain also can be subject to disciplinary action. As noted, many pain organizations have attempted to facilitate compassionate and effective pharmacologic cancer pain management.
The majority of patients with advanced cancer stages (III and IV) have pain, with 54% having pain that is at least of moderate intensity. American Academy of Pain Medicine, the American Pain Society, and the American Society of Addiction Medicine. Minozzi S, Amato L, Davoli M, Development of dependence following treatment with opioid analgesics for pain relief: a systematic.
Jarzyna D, Jungquist CR, Pasero C, et al, American Society for Pain Management Nursing: guidelines on monitoring for opioid-induced sedation and respiratory depression. How Do We Get Enough Physicians to Medically Manage The Difficult (High-dose Opioid) Pain Patient? To date, most treatments have focused on reduction of symptoms,6 and, in the case of diabetes, control or slowing of the progression of the underlying disease. Neuropathic pain occurs when normal signaling between adjacent nerve cells attenuates as a result of insufficient oxygen transport.
This defense mechanism also occurs upon exposure to environmental toxins, chemotherapeutic agents, military chemical weapons, insecticides, and other neurotoxic substances.
Signals of normal intensity can no longer bridge this newly widened gap, resulting in a loss of bioelectric integrity. These conductive minerals and neurotransmitters are delivered via the perfusion of adjacent tissues with fresh blood. This effect most likely is the result of ephatic firing, defined as some nerve signals being misdirected to nearby nerves.12-14 As the condition worsens, more signals are misdirected or suppressed, leading to increasingly unpleasant sensations such as stinging, burning, and pain. These conditions often result in poor tissue perfusion, insecure gait, balance problems, general muscle weakness, and other mobility issues.
Nerve conduction velocity (NCV) testing is less sensitive than A-delta NCS but can also measure all three fibers. Still, C fibers are known to have a primary influence in the development of the pathophysiology of diabetes. However, ENFD testing is rapidly becoming an accepted standard to measure afferent C fibers and unmyelinated A-delta fibers.18 Thermal evoked potentials and fMRI also can measure the function of C and A-delta fibers, but ENFD currently is the most practical method.

The prevalence, severity, and impact of painful diabetic peripheral neuropathy in type 2 diabetes.
Pain severity and the economic burden of neuropathic pain in the United States: BEAT Neuropathic Pain Observational Study.
Clinical Outcomes utilizing the Combined Electrochemical Treatment for Peripheral Neuropathy: A Retrospective Study from a Western Clinic. Induction of mitosis in mature neurons in central nervous system by sustained depolarization.
Usefulness of skin biopsies in the evaluation and management of patients with suspected small fiber neuropathy. Electric current and local anesthetic combination successfully treats pain associated with diabetic neuropathy. Glutamate uptake into astrocytes stimulates aerobic glycolysis: A mechanism coupling neuronal activity to glucose utilization. Vertical Health Media, LLC disclaims any liability for damages resulting from the use of any product advertised herein and suggests that readers fully investigate the products and claims prior to purchasing. But figuring out which drug will work best for a patient can be difficulta€”patients may have to switch from one therapy to another to see whether their symptoms improve. They are trying to understand why TNFi agents fail for some patients and work for others, and the answer may lay in a very specific genetic markera€”HS1,2Aa€”a polymorphism associated with several autoimmune chronic inflammatory conditions. Using Ingenuity Pathway Analysis (IPA) software, the researchers were able to investigate the biological networks related to the polymorphism based on the 2 distinct genotypes.
Such findings further explain the potential significance of the HS1,2A polymorphism in assessing and even predicting a patienta€™s disease severity and response to intervention.
Non-responders to the drug, however, showed no noticeable differences in gene expression from baseline to 3 months. A trial of etanercept, a recombinant tumor necrosis factor receptor: Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. Adalimumab, a fully human anti-tumor necrosis factor I± monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: The ARMADA trial. Evidence for differential acquired drug resistance to anti-TNF agents in rheumatoid arthritis. Evolution of human IgH3'EC duplicated structures: Both enhancers HS1,2 are polymorphic with variation of transcription factor's consensus sites. Signaling, inflammation and arthritis: NF-kappaB and its relevance to arthritis and inflammation. Allele *2 of the HS1,2A enhancer of the Ig regulatory region associates with rheumatoid arthritis. Using the data from this study, the estimated cost of each chronic condition was calculated by multiplying the average cost per patient for each condition by the prevalence of the condition. The problem is that the small percentage of patients who go on to develop chronic pain are extraordinarily expensive to treat. Following the onset of a painful condition, the treatment of acute painful conditions is driven by medical factors. Routine diagnostics, medications, restriction of activity, and physical therapy are often used. It has been theorized previously that biopsychosocial pain disorders occur in different forms with a distinct natural history. As noted elsewhere however, biopsychosocial disorders occur in different forms.9 For example, in some cases, there is a clear pathophysiological explanation for the patienta€™s pain.
Recent classification criteria assist in the differentiation of PMR from several possible mimics of this disease.
The lifetime risk of adult-onset rheumatoid arthritis and other inflammatory autoimmune rheumatic diseases.
Erythrocyte sedimentation rate and C-reactive protein in the evaluation of disease activity and severity in polymyalgia rheumatica: a prospective follow-up study. Repetitive 18-fluorodeoxyglucose positron emission tomography in isolated polymyalgia rheumatica: a prospective study in 35 patients. Ultrasound of proximal upper extremity arteries to increase the diagnostic yield in large-vessel giant cell arteritis. Incidence of temporal arteritis in patients with polymyalgia rheumatica: a prospective study using colour Doppler ultrasonography of the temporal arteries. Clinical outcomes, quality of life, and diagnostic uncertainty in the first year of polymyalgia rheumatica.
Prednisone plus methotrexate for polymyalgia rheumatica: a randomized, double-blind, placebo-controlled trial.
Can methotrexate be used as a steroid sparing agent in the treatment of polymyalgia rheumatica and giant cell arteritis? Long-term follow-up of polymyalgia rheumatica patients treated with methotrexate and steroids. Infliximab plus prednisone or placebo for the initial treatment of polymyalgia rheumatica: a randomized trial. Additionally there is very little literature detailing whether treating beyond 4 weeks is beneficial. A retrospective analysis was performed via chart review on 40 patients in an outpatient Veterana€™s Affairs (VA) Physical Medicine and Rehabilitation Clinic in Long Beach, California.
Exclusion criteria comprised of any patient who did not take a PRFE device home after the initial office trial. A treatment applicator pad was placed directly over the site of maximal pain and a nonionizing, nonthermal carrier frequency energy was emitted at 27.12 MHz for 30 minutes.
Patients were then instructed to return to the clinic within 4 weeks to evaluate their pain and activities of daily living (ADL). Numeric pain scores were also collected via chart review, which included pain before initial trial (initial), 30 minutes after trial (post-trial), 4 weeks, and 8 weeks. Therefore 40 patients completed the initial trial, which was reduced to 36 subjects at 4 weeks and 21 subjects at 8 weeks. Statistical analysis using the Wilcox Signed Rank Test for a nonparametric two-tailed test was performed across the 40 patients. Each of the patients treated had at least one diagnosis and 3 patients met criteria for two diagnoses that explained their pain symptoms (eg, spinal stenosis and lumbar radiculopathy).
Nevertheless, all 10 diagnoses showed a generalized trend of improvement over time with few exceptions: slight worsening of failed back syndrome from post-trial to 4 weeks, no change in diabetic neuropathy during post-trial to 8 weeks, no change in knee osteoarthritis at 4 and 8 weeks, and some worsening of postsurgical abdominal pain at 8 weeks (Figure 2).
PROVANT Wound-Closure System accelerates closure of pressure wounds in a randomized, double-blind, placebo-controlled trial. Electromagnetic fields instantaneously modulate nitric oxide signaling in challenged biological systems.
Activation of endogenous opioid gene expression in human keratinocytes and fibroblasts by pulsed radiofrequency energy fields. Pulsed radio frequency energy field treatment of cells in culture: Increased expression of genes involved in angiogenesis and tissue remodeling during wound healing. A pulsing electric field (PEF) increases human chondrocyte proliferation through a transduction pathway involving nitric oxide signaling. Mechanisms of analgesic action of pulsed radiofrequency on adjuvant-induced pain in the rat: roles of descending adrenergic and serotonergic systems. Transcutaneous pulsed radiofrequency treatment for patients with shoulder pain booked for surgery: a double-blind, randomized controlled trial. Transcutaneous pulsed radiofrequency treatment in patients with painful knee awaiting total knee joint replacement.
Use of pulsed radio frequency energy in the effective treatment of recalcitrant plantar fasciitis: Six case histories. Effects of pulsed electromagnetic fields on postoperative pain: a double-blind randomized pilot study in breast augmentation patients. Heel neuroma: the enigma of recalcitrant heel pain and an innovative approach highlighting sixty surgical cases and a review of two hundred and fifty seven symptomatic but non-surgical cases.
Electrophysical agents-contraindications and precautions: an evidence-based approach to clinical decision making in physical therapy. Pulsed radiofrequency versus conventional transcutaneous electrical nerve stimulation in painful shoulder: a prospective, randomized study. Many cancer patients are living longer, shifting pain management from a focus on acute pain to chronic pain. Pain management issues are infrequently highlighted at hospital rounds or educational conferences, resulting in providersa€™ lack of opioid-prescribing skills including equianalgesic opioid doses. For persistent pain, which requires an around-the-clock (ATC) medication regimen, it is preferable to use long-acting formulations to improve patient compliance with potentially less euphoric side effects and reduced concerns of behavior aberrancies. Opioids should be considered first-line therapy for patients with moderate to severe pain related to cancer, acquired immune deficiency syndrome, or other life-threatening illness.
The "red flag" for investigation of active cancer-related pain is spontaneous onset, particularly with intensification during sleep or lying down. Extended-release (ER) and long-acting (LA) opioid analgesics risk evaluation and mitigation strategy (REMS). Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC. Opioids in palliative care: safe and effective prescribing of strong opioids for pain in palliative care of adults.

Dose-titration, multicenter study of oral transmucosal fentanyl citrate for the treatment of breakthrough pain in cancer patients using transdermal fentanyl for persistent pain. Prevalence and characteristics of breakthrough pain in opioid-treated patients with chronic noncancer pain.
Predicting aberrant behaviors in opioid-treated patients: preliminary validation of the Opioid Risk Tool. Conjoint screening questionnaires for alcohol and other drug abuse: criterion validity in primary care practice.
Development of a self-report screening instrument for assessing potential opioid medication misuse in chronic pain patients. The SISAP: a new screening instrument for identifying potential opioid abusers in the management of chronic nonmalignant pain within general medical practice.
Predicting aberrant drug behavior in patients treated for chronic pain: importance of abuse history. The addiction behaviors checklist: validation of a new clinician-based measure of inappropriate opioid use in chronic pain. Reality and responsibility: a commentary on the treatment of pain and suffering in a drug-using society.
Universal precautions in pain medicine: a rational approach to the treatment of chronic pain. Contraction, which is one such defense mechanism, causes a generalized shrinking of the nerve cells and a widening of the synaptic cleft between these cells.
They are kept in suspension by the periodic ionization of successfully transmitted nerve signals across the junction. From a diagnostic standpoint, specific neurodiagnostic testing can directly measure this effect, as the increased voltage threshold necessary to fire enough nerve axons for the patient to a€?feela€? sensation normally.
A-delta function is effectively measured by A-delta NCS with 95% accuracy.15 Efferent C fiber function, which is a primary pathology, is best assayed by quantitative sensory testing (QST) such as sweat testing (Sudoscan), thermography, and possibly fMRI, and will be considered in future studies. Poster Presentation at: the 18th Annual International Spine Intervention Society Meeting, Las Vegas, NV, July 2008. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group.
A chronic pain category was formed by combining patients with complaints of back pain, neck pain, headaches or facial pain.
One study found that 10% of back pain cases with chronic pain accounted for around 79% of the costs,6 which would make this group of chronic patients 34 times more expensive to treat than the other patients.
Although the entry point for evaluation and treatment of pain conditions may be the emergency room or urgent care physician, it is typically the primary care physician (PCP) who manages the acute phase of treatment.
During this phase, psychological and social factors generally play a much more limited role. This natural history often involves a a€?downward spiral,a€? in which a medical condition becomes progressively more enmeshed with psychosocial complications.9 Using this model, one of the first signs that a biopsychosocial pain disorder is developing in the subacute phase may be an observed deviation from the expected course of recovery.
The patient may have sustained a catastrophic injury, or there may be an identifiable disease process.
Chronic pain and biopsychosocial disorders: The BHI 2 approach to classification and assessment. Occupational medicine practice guidelines : evaluation and management of common health problems and functional recovery of workers. Limbically augmented pain syndrome (LAPS): kindling, corticolimbic sensitization, and the convergence of affective and sensory symptoms in chronic pain disorders. Depression and medication adherence in outpatients with coronary heart disease: findings from the Heart and Soul Study. Incorporation of cognitive-behavioral treatment into the medical care of chronic low back patients: a controlled randomized study in German pain treatment centers.
The impact of marital relationship on the rehabilitation process in a group of women with long-term musculoskeletal disorders.
Behavioral treatment of chronic pain: the spouse as a discriminative cue for pain behavior.
Cognitive behavior therapy and pharmacotherapy for insomnia: a randomized controlled trial and direct comparison.
Discographic, MRI and psychosocial determinants of low back pain disability and remission: a prospective study in subjects with benign persistent back pain. Prospective controlled study of the development of lower back pain in previously asymptomatic subjects undergoing experimental discography. Advanced imaging can aid in diagnosis, and ultrasonography appears to be the most suitable and cost-effective modality.
Our goal for performing this review was to determine whether PRFE was beneficial for chronic pain and if additional benefit occurred with those who received 8 week treatment. Internal Review Board (IRB) approval was attained through the Southern California Institute for Research and Education before collecting any data. It should be noted that the treating physician did not offer this treatment to anyone with active infection, cancer, or an implantable electronic stimulating device.
If the patienta€™s pain improved but their ADL had not, they had the option to extend their trial for an additional 4 weeks.
This was scored on a numeric rating scale of 0-10 with 0 reflecting no pain, 1-3 mild pain and mild interference on ADL, 4-6 moderate pain and moderate interference on ADL, and 7-10 severe pain and inability to perform ADL. Patient dropout occurred for various reasons: pain resolved with treatment, twice daily frequency was inconvenient, insufficient efficacy, and patient inability to access electricity to run device. As a result, the 40 patients had a total of 43 diagnoses after being grouped into the following categories: rotator cuff tear, failed back syndrome, myofascial pain, radiculopathy, spinal stenosis, diabetic neuropathy, knee osteoarthritis, lumbar facet arthritis, ankle osteoarthritis, and postsurgical abdominal pain (Table 1).
However it should be noted that these exceptions occurred only in diagnoses with low sample sizes of 3 or less, but regardless all diagnoses showed improvement from their initial pain scores. There also continues to be major concerns regarding the regulatory oversight of opioid prescribing, including a recent FDA hearing to reclassify hydrocodone as a DEA schedule II (as recently enacted in New York), which would allow labeling that limits the duration, allow dosing recommendations for opioids used for non-malignant pain, and propose criterion for labeling abuse-deterrent formulations. There are FDA-mandated risk evaluation and mitigation strategies (REMS) aimed at providers, patients, and pharmacists to ensure proper education about these medications.8 Many of the concepts presented in this article also may be applied to non-malignant pain. However, these formulations tend to be more expensive and have a greater risk of causing sleep-disordered breathing (central sleep apnea).9 The dosing frequency may be increased, if necessary, for titration of analgesic control. They should also be considered for any appropriate patients with moderate to severe non-cancer pain.5 This concept has been endorsed by many national and international pain societies including the World Health Organization (WHO). A decision to initiate opioid therapy is based on the severity of the pain, anticipated efficacy, minimization of side effects, stratification of risk of potential aberrancy, and the reasonable alternatives, both pharmacologic and nonpharmacologic. Clinical guidelines and procedures for the use of methadone in the maintenance treatment of opioid dependence.
Using this approach, the cost of treating chronic pain exceeded the costs of all other chronic conditions that were assessed, including heart disease, respiratory disease, or cancer (see Table 1).
Similarly, another study found that 5% of chronic back pain cases accounted for about 85% of all medical costs for this condition,7 making this group of chronic patients 57 times more expensive to treat. The PCP generally begins with conservative care and, in most cases, patients recover as expected.
If, after a month or so, the severity of the reported pain or disability is difficult to explain given the objective medical findings, this increases the risk that the acute condition may be evolving into a chronic biopsychosocial pain disorder. A patient who has a life changing, painful medical condition will often need to contend with the social impact of being disabled.
Evidence arising from the Royal College of General Practitioners’ Oral Contraception study. Patients with PMR should be followed longitudinally because some are eventually reclassified as having rheumatoid arthritis or GCA.
Inclusion criteria comprised of every patient that received PRFE treatment within the principal investigatora€™s patient population at the VA. It is important to note that no subject was reported to discontinue treatment secondary to adverse side effects. To treat breakthrough cancer pain (BTP), additional analgesics are prescribeda€”including short-acting, oral, or rectal opioidsa€”with supplemental rapid-onset opioids, currently classified as transmucosal immediate-release fentanyl (TIRF) products (Table 1). For refractory cancer pain patients, the subcutaneous route (avoiding intramuscular administration) can be effective for the administration of morphine and hydromorphone, and it should be considered a viable choice for appropriate patients unable to receive opioids by oral or transdermal routes, particularly if they are in institutions. If a patient with a mild injury appears severely depressed or unreasonably angry in the days following an accident, demands a high level of opioids, refuses examination, or is grossly noncompliant, the role of psychosocial complications should be explored. Given this kind of medical condition, some have commented that it is surprising when depression does not occur.12 This associated distress can lead to additional stress-related symptoms, and to a worsening of the patienta€™s pain and suffering. Disease- and treatment-related morbidity remains significant; however, mortality is not increased in patients with PMR. Intravenous (IV) infusion should be considered when subcutaneous administration is contraindicated (peripheral edema, coagulation disorders, poor peripheral circulation, and need for high volumes and doses).
GCs are the mainstay of treatment, but the ongoing evaluation of biologic agents may provide alternative approaches to management in the near future. When they do occur, they should not be overlooked as they may indicate that a biopsychosocial condition is already starting to evolve.

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