Recent Advances in Management of Neuropathic, Nociceptive, and Chronic Pain: A Narrative Review with Focus on Nanomedicine, Gene Therapy, Stem Cell Therapy, and Newer Therapeutic Options.

PURPOSE OF REVIEW: This manuscript summarizes novel clinical and interventional approaches in the management of chronic, nociceptive, and neuropathic pain. RECENT FINDINGS: Pain can be defined as a feeling of physical or emotional distress caused by an external stimulus. Pain can be grouped into distinct types according to characteristics including neuropathic pain, which is a pain caused by disease or lesion in the sensory nervous system; nociceptive pain, which is pain that can be sharp, aching, or throbbing and is caused by injury to bodily tissues; and chronic pain, which is long lasting or persisting beyond 6 months. With improved understanding of different signaling systems for pain in recent years, there has been an upscale of methods of analgesia to counteract these pathological processes. Novel treatment methods such as use of cannabinoids, stem cells, gene therapy, nanoparticles, monoclonal antibodies, and platelet-rich plasma have played a significant role in improved strategies for therapeutic interventions. Although many management options appear to be promising, extensive additional clinical research is warranted to determine best practice strategies in the future for clinicians.

Nociplastic pain: towards an understanding of prevalent pain conditions.

Nociplastic pain is the semantic term suggested by the international community of pain researchers to describe a third category of pain that is mechanistically distinct from nociceptive pain, which is caused by ongoing inflammation and damage of tissues, and neuropathic pain, which is caused by nerve damage. The mechanisms that underlie this type of pain are not entirely understood, but it is thought that augmented CNS pain and sensory processing and altered pain modulation play prominent roles. The symptoms observed in nociplastic pain include multifocal pain that is more widespread or intense, or both, than would be expected given the amount of identifiable tissue or nerve damage, as well as other CNS-derived symptoms, such as fatigue, sleep, memory, and mood problems. This type of pain can occur in isolation, as often occurs in conditions such as fibromyalgia or tension-type headache, or as part of a mixed-pain state in combination with ongoing nociceptive or neuropathic pain, as might occur in chronic low back pain. It is important to recognise this type of pain, since it will respond to different therapies than nociceptive pain, with a decreased responsiveness to peripherally directed therapies such as anti-inflammatory drugs and opioids, surgery, or injections.

Deep Brain Stimulation for Facial Pain.

Electro-modulation of subcortical deep brain structures by surgically implanted electrodes is now standard evidence-based treatment for movement disorders such as Parkinson's disease and essential tremor and is approved for dystonia and obsessive-compulsive disorder under a humanitarian exemption. Historically, deep brain stimulation (DBS) for multiple indications has demonstrated acceptable complication rates, rare mortality, and reducing morbidity as the technology and the techniques of its application have advanced. DBS for the amelioration of pain has been performed since the early 1950s, and became widely used in the 1970s, when targeting the somatosensory thalamus was shown to be efficacious for intractable pain syndromes including facial pain. The technique fell out of favour in the late 1990s after 2 multicentre trials failed to meet end-point criteria. Since these trials, DBS for pain has remained for investigational or "off-label" use. Criticisms from previous literature have involved unsuitability of patient selection, as well as inconsistencies in neurosurgical technique. Clinical success with DBS for facial pain has been for the treatment of a variety of chronic neuropathic and nociceptive pain syndromes; including trigeminal neuropathy, post-herpetic neuralgia, deafferentation facial pain, "atypical" facial pain, cluster headaches and other trigeminal autonomic cephalalgias, as well as head and neck pathologies, most often which have been resistant to all other 1st- and 2nd-line medical and surgical treatments, when DBS has become a "last treatment option." An enhanced understanding of the mechanisms of action of DBS for pain will enhance outcome, and appropriately prescribe evolving novel nuclear brain targets.

Postoperative pain pathophysiology and treatment strategies after CRS + HIPEC for peritoneal cancer.

BACKGROUND: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment choice for peritoneal cancer. However, patients commonly suffer from severe postoperative pain. The pathophysiology of postoperative pain is considered to be from both nociceptive and neuropathic origins. MAIN BODY: The recent advances on the etiology of postoperative pain after CRS + HIPEC treatment were described, and the treatment strategy and outcomes were summarized. CONCLUSION: Conventional analgesics could provide short-term symptomatic relief. Thoracic epidural analgesia combined with opioids administration could be an effective treatment choice. In addition, a transversus abdominis plane block could also be an alternative option, although further studies should be performed.

Assessment and Management of Chronic Pain in the Seriously Ill.

The intent of this article is to help clinicians to have practical knowledge and skills related to both assessment and pharmacotherapy of chronic pain in the seriously ill patients. Treating patients with chronic pain and progressive disease should include assessment of "total pain" (physical, psychological, and spiritual suffering) and the care givers as part of treatment team. Effective management of chronic pain starts with thorough assessment and diagnosis of the pain syndrome. A worldwide consensus endorses use of multimodal approach and opioid pharmacotherapy as the mainstay approach to moderate to severe pain in cancer and pain associated with serious illness.

Clinical Decision-Making in Chronic Spine Pain: Dilemma of Image-Based Diagnosis of Degenerative Spine and Generation Mechanisms for Nociceptive, Radicular, and Referred Pain.

BACKGROUND: Spine-related pain is a complex heterogeneous condition. Excessive reliance on radiological imaging might lead to overdiagnosis of incidental asymptomatic spinal changes and unnecessary surgery. Approaches to the clinical management of spine pain should (1) identify pain generators, types, patterns, and mechanisms; (2) confirm clinical suspension with a diagnostic injection; and (3) ensure that treatment is aimed at controlling pain and improving patient function rather than image-based surgical success. METHOD: This case series (7 cases) discusses commonly seen clinical presentation of spine pain analytically, with illustrations of possible pain generators, mechanisms, pathways, and pain types. Each case discusses pain types and location (axial nociceptive, referred, and radicular neuropathic), generators (degenerated disc, herniated disc, facet joint, and sacroiliac joint), pathways (sinuvertebral ventral ramus and medial and lateral branches dorsal ramus), and radiculopathy versus radicular pain, elaborating on coccydynia and cervicogenic headaches, epimere versus hypomere muscle embryology, function, innervation, and role in spine-related pain. RESULTS: Multiple pain generators might coexist in the same patient causing mixed pain types and referral patterns with multiple mechanisms and pathways. History review, physical examination, and diagnostic injections are the mainstays of diagnosis. CONCLUSIONS: Image-detected spondylosis might be an asymptomatic process. Clinical presentation is related to stenosis or pain. The mechanism of pain is related to compression, inflammation, or microinstability. Spine pain can be nociceptive axial, neuropathic radicular, and/or referred pain. Although image findings are helpful in radicular neuropathic pain from disc herniation, they are unreliable in nociceptive pain, and correlation with clinical and diagnostic injections is mandatory.

Intrathecal administration of human bone marrow mesenchymal stem cells genetically modified with human proenkephalin gene decrease nociceptive pain in neuropathic rats.

Background: Mesenchymal stem cell (MSC) has been one of the potential tools in neuropathic pain therapy; however, the augmented efficacy may be expected when they are modified with human proenkephalin (hPPE) gene. In the current study, the antinociceptive effect of human bone marrow stem cells (hBMSCs) engineered with hPPE gene (hPPE-hBMSCs) on sciatic nerve chronic constriction injury (CCI)-induced neuropathic pain in rats was investigated. Methods: Primary-cultured hBMSCs were passaged and modified with hPPE, and the cell suspensions (6 × 106) were then intrathecally injected into a rat model of CCI. Paw mechanical withdrawal threshold and paw withdrawal thermal latency were measured before and after CCI surgery. The effects of hPPE gene transfer on hBMSCs bioactivity were analyzed in vitro and in vivo. Results: No changes were observed in the surface phenotypes and differentiation of hBMSCs after gene transfer. The hPPE-hBMSC group showed improved paw mechanical withdrawal threshold and paw thermal withdrawal latency values on the ipsilateral side of rats with CCI from day 9 post-surgery, and the analgesic effect was reversed by naloxone. Leucine-enkephalin (L-EK) secretion was augmented in the hPPE-engineered hBMSC group. Conclusions: The intrathecal administration of BMSCs modified with hPPE gene can effectively relieve pain caused by chronic constriction injury in rats and might be a potentially therapeutic tool for neuropathic pain in humans.

Changes in Dorsal Root Ganglion Gene Expression in Response to Spinal Cord Stimulation.

BACKGROUND AND OBJECTIVES: Spinal cord stimulation (SCS) has been shown to influence pain-related genes in the spinal cord directly under the stimulating electrodes. There is limited information regarding changes occurring at the dorsal root ganglion (DRG). This study evaluates gene expression in the DRG in response to SCS therapy. METHODS: Rats were randomized into experimental or control groups (n = 6 per group). Experimental animals underwent spared-nerve injury, implantation of lead, and continuous SCS (72 hours). Behavioral assessment for mechanical hyperalgesia was conducted to compare responses after injury and treatment. Ipsilateral DRG tissue was collected, and gene expression quantified for interleukin 1b (IL-1b), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), GABA B receptor 1 (GABAbr1), substance P (subP), Integrin alpha M (ITGAM), sodium/potassium ATP-ase (Na/K ATPase), fos proto-oncogene (cFOS), serotonin receptor 3A (5HT3r), galanin (Gal), vasoactive intestinal peptide (VIP), neuropeptide Y (NpY), glial fibrillary acidic protein (GFAP), and brain derived neurotropic factor (BDNF) via quantitative polymerase chain reaction. Statistical significance was established using analysis of variance (ANOVA), independent t tests, and Pearson correlation tests. RESULTS: Expression of IL-1b and IL-6 was reversed following SCS therapy relative to the increase caused by the injury model. Both GABAbr1 and Na/K ATPase were significantly up-regulated upon implantation of the lead, and SCS therapy reversed their expression to within control levels. Pearson correlation analyses reveal that GABAbr1 and Na/K ATPase expression was dependent on the stimulating current intensity. CONCLUSIONS: Spinal cord stimulation modulates expression of key pain-related genes in the DRG. Specifically, SCS led to reversal of IL-1b and IL-6 expression induced by injury. Interleukin 6 expression was still significantly larger than in sham animals, which may correlate to residual sensitivity following continuous SCS treatment. In addition, expression of GABAbr1 and Na/K ATPase was down-regulated to within control levels following SCS and correlates with applied current.

TRESK contributes to pain threshold changes by mediating apoptosis via MAPK pathway in the spinal cord.

The mechanism underlying neuropathic pain (NP) is complex and has not been fully elucidated. The TWIK-related spinal cord K+ (TRESK) is the major background potassium current in dorsal root ganglia (DRG), we found that mitogen-activated protein kinase (MAPK) signal pathway were activated in spinal cord accompanied by TRESK down regulation in response to NP. Therefore, we investigated whether TRESK mediates inflammation and apoptosis by MAPK pathway in the spinal cord of NP rats. SNI rats exhibited reduced TRESK expression in DRG and spinal cord and higher sensitivity to mechanical stimuli but no effect on thermal stimuli. Intrathecal injections of TRESK overexpressing adenovirus alleviated mechanical allodynia, inhibited phosphorylation of extracellular signal-regulated kinase (ERK) and p38, and decreased inflammatory reactions and apoptosis in the spinal cords of SNI rats. Down regulation of TRESK in DRG and spinal cord was detected in normal rats after intrathecal TRESK shRNA lentivirus injection, which induced mechanical allodynia but had no effect on pain thresholds for heat stimulation. Phosphorylated ERK and p38 were increased in the spinal cord. Intrathecal injection of an ERK antagonist (PD98059) and p38 antagonist (SB203580) prevented ERK and p38 activation in the spinal cord and mechanical allodynia induced by TRESK shRNA lentivirus. In conclusion, our study clearly demonstrated an important role for TRESK in NP and that TRESK regulation contributes to pain sensitivity mediates inflammation and apoptosis by ERK and p38 MAPK signaling in the spinal cord.

[Physiotherapy of cancer patients]. / Daganatos betegek fizioterápiája.

Physiotherapy of cancer patients is one of the most controversial issues in our country. Malignant diseases are firstly mentioned as a contraindication of physiotherapy. Until now, physiotherapy was not suggested (or only in limited accessibility) for those patients who had malignant disease in medical history. International medical practice was less restrictive in managing this topic. The development of imaging techniques put this question in a new light. On the basis of evidence, the majority of articles have reported beneficial effects of physiotherapy in cancer patients, and only few articles mentioned it as harmful. Of course, each patient requires an individual assessment, however, if we exclude the possibility of tumor recurrence and metastasis, most of physiotherapy procedures can be used safely. One of the aims of this review is to support the physicians' decisions when to prescribe treatments, in such a way, that more patients could receive physiotherapy. Orv. Hetil., 2016, 157(31), 1224-1231.

Pain management in patients with vascular disease.

Vascular disease covers a wide range of conditions, including arterial, venous, and lymphatic disorders, with many of these being more common in the elderly. As the population ages, the incidence of vascular disease will increase, with a consequent increase in the requirement to manage both acute and chronic pain in this patient population. Pain management can be complex, as there are often multiple co-morbidities to be considered. An understanding of the underlying pain mechanisms is helpful in the logical direction of treatment, particularly in chronic pain states, such as phantom limb pain or complex regional pain syndrome. Acute pain management for vascular surgery presents a number of challenges, including coexisting anticoagulant medication, that may preclude the use of regional techniques. Within the limited evidence base, there is a suggestion that epidural analgesia provides better pain relief and reduced respiratory complications after major vascular surgery. For carotid endarterectomy, there is again some evidence supporting the use of local anaesthetic analgesia, either by infiltration or by superficial cervical plexus block. Chronic pain in vascular disease includes post-amputation pain, for which well-known risk factors include high pain levels before amputation and in the immediate postoperative period, emphasizing the importance of good pain control in the perioperative period. Complex regional pain syndrome is another challenging chronic pain syndrome with a wide variety of treatment options available, with the strongest evidence being for physical therapies. Further research is required to gain a better understanding of the underlying pathophysiological mechanisms in pain associated with vascular disease and the best analgesic approaches to manage it.

Abnormal feeding behaviour in spinalised rats is mediated by hypothalamus: Restorative effect of exposure to extremely low frequency magnetic field.

STUDY DESIGN: Experimental study. OBJECTIVES: To investigate the role of hypothalamus in abnormal feeding behaviour after spinal cord injury (SCI) and the effect of exposure to extremely low frequency magnetic field (ELF-MF) on it. SETTING: India. METHODS: Male Wistar rats (n=44) were divided into Sham (laminectomy), SCI (complete transection of T13 spinal cord), SCI+MF (ELF-MF exposure to SCI rats), VMHL (lesion of ventromedial hypothalamus; VMH), SCI+VMHL (VMHL after SCI) and SCI+VMHL+MF (ELF-MF exposure to SCI+VMHL rats) groups. Food intake (FI), water intake (WI), calorie intake (CI), body weight (BWT), taste preference and sucrose-induced biphasic (SIB) response to noxious stimulus were studied pre and post surgery. Neuronal activity at VMH was assessed by c-Fos immunohistochemistry. The extent of neuronal degeneration and regeneration in spinal cord was assessed microscopically. RESULTS: Data revealed post-SCI decrease in FI, WI, CI and BWT, preference for sodium chloride and citric acid, prolonged analgesic phase of SIB and increased c-Fos immunoreactivity in VMH of SCI rats vs Sham rats. VMH lesion increased FI, WI, CI, BW, preference for sweet tastants and abolished SIB, whereas in SCI+VMHL rats it abolished the effects of SCI on these parameters indicating probable involvement of VMH in SCI-induced alteration in feeding behaviour. Exposure to MF improved the study parameters in SCI rats and reduced the c-Fos immunoreactivity in VMH besides reduction in lesion volume, greater myelination and neuronal regeneration at SCI site. CONCLUSION: SCI influences VMH, leading to alteration in feeding behaviour, which is improved by exposure to ELF-MF.

Rethinking chronic pain in a primary care setting.

Chronic pain substantially impacts patient function and quality of life and is a burden to society at large in terms of increased health care utilization and loss of productivity. As a result, there is an increasing recognition of chronic pain as a public health crisis. However, there remains wide variability in clinical practices related to the prevention, assessment, and treatment of chronic pain. Certain fundamental aspects of chronic pain are often neglected including the contribution of the psychological, social, and contextual factors associated with chronic pain. Also commonly overlooked is the importance of understanding the likely neurobiological mechanism(s) of the presenting pain and how they can guide treatment selection. Finally, physicians may not recognize the value of using electronic medical records to systematically capture data on pain and its impact on mood, function, and sleep. Such data can be used to monitor onset and maintenance of treatments effects at the patient level and evaluate costs at the systems level. In this review we explain how these factors play a critical role in the development of a coordinated, evidence-based treatment approach tailored to meet specific needs of the patient. We also discuss some practical approaches and techniques that can be implemented by clinicians in order to enhance the assessment and management of individuals with chronic pain in primary care settings.

Management of somatic pain induced by treatment of head and neck cancer: Postoperative pain. Guidelines of the French Oto-Rhino-Laryngology--Head and Neck Surgery Society (SFORL).

OBJECTIVE: To present the guidelines of the French Oto-Rhino-Laryngology--Head and Neck Surgery Society (SFORL) concerning the management of somatic pain induced by the treatment of head and neck cancer, and in particular the management of early and late post-surgical pain. METHODS: A multidisciplinary work group conducted a review of the scientific literature on the study topic. An editorial group subsequently read the resulting guidelines before validation. RESULTS: It is recommended to prevent onset of pain caused by malpositioning on the operating table, as well as pain related to postoperative care. During surgery, it is recommended to spare nerve and muscle structures as far as possible to limit painful sequelae. Management of early postoperative pain upon tumor resection and flap harvesting sites requires patient-controlled analgesia by morphine pump. Physical therapy is recommended after flap harvesting to minimize painful sequelae. CONCLUSION: Preventive and curative measures should be undertaken for appropriate management of post-surgical pain in the treatment of head and neck cancers.

Management of somatic pain induced by head-and-neck cancer treatment: definition and assessment. Guidelines of the French Oto-Rhino-Laryngology- Head and Neck Surgery Society (SFORL).

OBJECTIVES: The authors present the guidelines of the French Oto-Rhino-Laryngology- Head and Neck Surgery Society (Société Française d'Oto-rhino-Laryngologie et de Chirurgie de la Face et du Cou [SFORL]) for the management of somatic pain induced by head-and-neck cancer treatment, and in particular the instruments needed for the definition and initial assessment of the various types of pain. METHODS: A multidisciplinary work group was entrusted with a review of the scientific literature on the above topic. Guidelines were drawn up, based on the articles retrieved and the group members' individual experience. They were then read over by an editorial group independent of the work group. The final version was established in a coordination meeting. The guidelines were graded as A, B, C or expert opinion, by decreasing level of evidence. RESULTS: The priority is to eliminate tumoral recurrence when pain reappears or changes following head-and-neck cancer treatment. Neuropathic pain screening instruments and pain assessment scales should be used to assess pain intensity and treatment efficacy. Functional rehabilitation sessions should be prescribed to reduce musculoskeletal pain and prevent ankylosis and postural disorder. Psychotherapy and mind-body therapy, when available, should be provided in case of chronic pain. In case of recalcitrant complex pain, referral should be made to a multidisciplinary pain structure. CONCLUSION: The management of somatic pain induced by head-and-neck cancer treatment above all requires identifying and assessing the intensity of the various types of pain involved, their functional impact and their emotional component.

Antinociceptive effect of intrathecal microencapsulated human pheochromocytoma cell in a rat model of bone cancer pain.

Human pheochromocytoma cells, which are demonstrated to contain and release met-enkephalin and norepinephrine, may be a promising resource for cell therapy in cancer-induced intractable pain. Intrathecal injection of alginate-poly (l) lysine-alginate (APA) microencapsulated human pheochromocytoma cells leads to antinociceptive effect in a rat model of bone cancer pain, and this effect was blocked by opioid antagonist naloxone and alpha 2-adrenergic antagonist rauwolscine. Neurochemical changes of cerebrospinal fluid are in accordance with the analgesic responses. Taken together, these data support that human pheochromocytoma cell implant-induced antinociception was mediated by met-enkephalin and norepinephrine secreted from the cell implants and acting at spinal receptors. Spinal implantation of microencapsulated human pheochromocytoma cells may provide an alternative approach for the therapy of chronic intractable pain.

Efecto antinociceptivo del extracto etanólico de las hojas de Maytenus macrocarpa (Ruiz & Pav.) Briq. ôchuchuhuasiõ mediante la prueba de contorsiones abdominales en ratones / Antinociceptive effect of the ethanol extract of the leaves of Maytenus macrocarpa (Ruiz & Pav.) Briq. ôchuchuhuasiõ Through the Writhing Test in mice

Objetivo: Determinar el efecto y actividad antinociceptiva de las hojas de Maytenus macrocarpa (Ruiz & Pav) Briq. ôchuchuhuasiõ mediante la prueba de contorsiones abdominales en roedor. Material y Métodos: Se utilizaron 40 ratones albinos machos, con pesos medios de 25g, se empleó la prueba de contorsiones abdominales para determinar la actividad antinociceptiva. El grupo Control, no recibió ninguna sustancia. Se administró extracto etanólico de las hojas de M. macrocarpa (Ruiz & Pav.) Briq. 2000 mg/kg, Tramadol 10 mg/kg y Diclofenaco sódico 10 mg/kg. Las sustancias fueron administradas por la vía oral una hora antes de la inducción de dolor. Para la validación estadística se usó la prueba de Shapiro-Wilk, ANOVA de una cola, Tukey, y Newman-Keuls. Resultados: El número de contorsiones abdominales fue 41+/- 3.04, 27+/- 3.55, 9 +/- 4.14, y 18 +/- 2.65 respectivamente. El porcentaje de inhibición de la conducta nociceptiva fue: 0%, 34%, 77%, y 55%. La prueba de ANOVA de una vía, demostró diferencias estadísticas (p<0.05, IC 95%), y la prueba de Tukey y Newman-Keuls, demostraron diferencias significativas entre los grupos, frente al control. Conclusiones: Se comprobó el efecto antinociceptivo de las hojas de Maytenus macrocarpa (Ruiz & Pav.) Briq. ôchuchuhuasiõ, en dosis de 2000 mg/kg.

Objetives: To determine the effect and antinociceptive activity of the leaves of Maytenus macrocarpa (Ruiz & Pav ) Briq . ôChuchuhuasi ô by the writhing test in rodents. Material and Methods: 40 male albino mice were used, with average weights of 25g, the writhing test was used to determine the antinociceptive activity. The experimental groups were: Control; received no substance, ethanol extract of the leaves of M. macrocarpa Briq (Ruiz & Pav.) 2000 mg/kg, Tramadol 10 mg/kg and 10mg Sodium Diclofenac /kg. The substances were administered orally one hour before the induction of pain. For statistical validation the Shapiro -Wilk test, one-tailed ANOVA, Tukey, and Newman -Keuls was used. Results: Writhing number was 41 +/- 3.04, 27 +/- 3.55, 9 +/- 4.14, and 18 +/- 2.65 respectively. The inhibition percentage of the nociceptive behavior was: 0%, 34%, 77% and 55%. The test of one-way ANOVA showed statistical differences (p < 0.05, 95% CI), and the Tukey and Newman-Keuls test showed significant differences between groups versus control. Conclusions: Antinociceptive effect of the leaves of Maytenus macrocarpa (Ruiz & Pav.) Briq ôChuchuhuasiô was found at doses of 2000 mg/kg.

Generalised and regional soft tissue pain syndromes. The role of physical and rehabilitation medicine physicians. The European perspective based on the best evidence. A paper by the UEMS-PRM Section Professional Practice Committee.

One of the objectives of the Professional Practice Committee (PPC) of the Physical and Rehabilitation Medicine (PRM) Section of the Union of European Medical Specialists (UEMS) is the development of the field of competence of PRM physicians in Europe. To achieve this objective, UEMS PRM Section PPC has adopted a systematic action plan of preparing a series of papers describing the role of PRM physicians in a number of disabling health conditions, based on the evidence of effectiveness of PRM interventions. Generalised and regional soft tissue pain syndromes constitute a major problem leading to loss of function and disability, resulting in enormous societal burden. The aim of this paper is to describe the unique role of PRM physicians in the management of these disabling conditions that require not only pharmacological interventions but also a holistic approach including the consideration of body functions, activities and participation as well as contextual factors as described in the ICF. Evidence-based effective PRM interventions include exercise and multicomponent treatment including a psychotherapeutic intervention such as cognitive behavioural therapy (CBT) in addition to exercise, the latter based on strong evidence for reducing pain and improving quality of life in fibromyalgia syndrome (FMS). Balneotherapy, meditative movement therapies, and acupuncture have also been shown as efficacious in improving symptoms in FMS. Emerging evidence suggests the use of transcranial magnetic or direct current stimulation (rTMS or tDCS) in FMS patients with intractable pain not alleviated by other interventions. Graded exercise therapy and CBT are evidence-based options for chronic fatigue syndrome. The use of some physical modalities and manipulation for myofascial pain syndrome is also supported by evidence. As for complex regional pain syndrome (CRPS), strong evidence exists for rTMS and graded motor imagery as well as moderate evidence for mirror therapy. Interventional techniques such as blocks and spinal cord stimulation may also be considered for CRPS based on varying levels of evidence. PRM physicians' functioning oriented approaches on the assessment and management, adopting the ICF as a reference, may well meet the needs of patients with soft tissue pain syndromes, the common problems for whom are loss of function and impaired quality of life. Available evidence for the effectiveness of PRM interventions serves as the basis for the explicit role of PRM specialists in the management of these health conditions.

[Treatment of nociceptive pain in primary care setting]. / Traitement des douleurs chroniques par excès nociceptif en soins de premier recours.

The pharmacological treatment of chronic pains induced by an excess of nociception is mainly based on analgesics which are classified according to their pharmacological nature (not opioid/opioid) and to their power according to the three World Health Organization steps. Their use is founded on a strategy which differs from the nature of pain (cancer pain vs no cancer pain), in particular with regard to the use of the strong opioids.

Nonsurgical interventions for low back pain.

A variety of nonoperative interventions are available to treat back pain. Careful assessment, discussion, and planning need to be performed to individualize care to each patient. This article discusses good to fair evidence from randomized controlled trials that injection therapy, percutaneous intradiscal radiofrequency thermocoagulation, intradiscal electrothermal therapy, and prolotherapy are not effective. Evidence is poor from randomized controlled trials regarding local injections, Botox, and coblation nucleoplasty; however, with a focused approach, the right treatment can be provided for the right patient. To be more effective in management of back pain, further high-grade randomized controlled trials on efficacy and safety are needed.