It is known that the constant, gradual and steady activation of pre-sensorimotor cortices, by enhanced motor imaginary and visual tactile discrimination, can promote the functional restoring. According to this, very gentle active movements progressing from active range of motion are strongly recommended. The progressive desensitization induces greater range of motion, pain relief, better discrimination and function improvement.
In order to manage CRPS chronic pain, various medications and a wide range of non-invasive and invasive interventions are available [ 6 , 17 - 20 ].
However, high quality evidence is lacking for any routine recommendation [ 21 , 22 ]. Many drugs, from different pharmacological classes, have been proposed to treat CRPS pain such as corticosteroids, antiinflammatory drugs, anticonvulsants gabapentin, pregabalin and carbamazepine , tricyclic antidepressants desipramine, imipramine, amitriptyline and nortriptyline , selective serotonin reuptake inhibitors antidepressants sertraline, fluoxetine, citalopram and escitalopram , serotonin and norepinephrine reuptake inhibitors antidepressants duloxetine and venlafaxine , opioids painkillers morphine, tramadol, oxycodone, methadone, fentanyl , bisphosphonates drugs, N-methyl-D-aspartate antagonists ketamina, memantine and dextromethorphan , adrenergic drugs clonidina , PDE5 inhibitor tadafil , calcitonin, calcium channel blockers, beta-blockers, sympatholitic agents, sodium channel blocking agents lidocaine , GABA agonists baclofen.
Although many drugs are very helpful especially if associated to a rehabilitation program , none of them have promoted significant alterations in syndrome course [ 3 , 6 , 10 , 21 - 23 ]. The classical techniques of sympathetic activity blocking are still a subject of controversy and their real effectiveness has never been proved. There is low quality of evidence favoring ganglion blocks using local anesthetic or intravenous regional sympatholysis using guanethidine, bretylium or reserpine to improve pain or function.
Furthermore, controlled trials have never succeeded in proving the effectiveness of either guanethidine intravenous infusion or surgical sympathectomy, which sometimes are associated to high rates of adverse events [ 21 ]. In recent years, neuromodulation has been increasingly used as a new strategy to treat CRPS chronic pain though the evidences are still weak.
These procedures for pain relief are either non-invasive or invasive and most of the times are considered as last resort therapy for patients whose long-term treatment was ineffective. It involves modulation of all aspects of the painful experience by stimulating or inhibiting specific targets in the central nervous system as pain pathways relays or modulatory nucleus. Although invasive neuromodulation has been considered more efficient and powerful, it requires longer training, specialized staff and it is more costly.
RACGP - Repetitive transcranial magnetic stimulation
It also has high complication rates which are related to surgical procedures such as infections, equipment failures, local pain in the implantation site and the need of replacement of its components [ 24 - 26 ]. Currently, there is no consensus regarding the grade of recommendation for neuromodulation techniques in CRPS treatment. Many interventions have been assessed; however there is a wide range and contradictory conclusions from the major trials, systematic reviews and meta-analysis studies.
To draw a reliable conclusion, a critical analysis of these studies is necessary. The objective of this paper is to make a critical narrative review evaluating the quality of evidences regarding neuromodulation effectiveness in CRPS chronic pain treatment. In order to find the best evidence level of each neuromodulation method, we have used key-words referring to neuromodulation effectiveness in CRPS treatment to select studies published in Medline, Lilacs and Cochrane Library databases.
All articles considered relevant were reviewed by two independently researchers to assign the level of evidence if they had English abstract and have described neuromodulation as a primary treatment. It has included randomized controlled trials, meta-analyses studies, systematic or narrative reviews, prospective and retrospective case series and case-reports. A third researcher was consulted in doubtful cases to draw a final conclusion. The levels of evidence and recommendation grades which were have used here were in agreement with Phillips [Oxford Centre for Evidence-based Medicine — Levels of Evidence] [ 27 ] Table 2.
Therapeutic rTMS in Neurology
After excluding articles that were not related to the topic and those where the disease, treatment or results were improperly described; thirty-nine articles were finally reviewed and graded Appendix 1. All randomized controlled trial, meta-analyses and systematic reviews studies found were included. Repetitive casuistic in different articles were reviewed and graded the main study. Thirteen prospective case series and seven casereports considered relevant because of the absence of better evidences were also included. No study approaching neuromodulation as CRPS pain primary treatment was graded as level A of evidence.
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Every other approach has got either grade C or D level of recommendation. Currently, the recommendation grades of many neuromodulation modalities to treat CRPS based on evidences are controversial. The best evidences and the highest degree of recommendation refers to SCS in treating refractory patients, although assigned degrees range from grade A28 to grade C In fact, carrying out a critical assessment of literature, there is no level 1 study which confers grade A of recommendation for any method of neuromodulation in the CRPS treatment.
Furthermore, the clinical effects do not appear to be significant to change either syndrome development or quality of life.
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Even multiple-session of rTMS did not consistently reveal to be effective [ 21 , 31 , 32 ]. It is possible that repeated sessions held periodically could be more effective, but at this time there is no high quality trial addressing this question. Despite rTMS be considered a simple, inexpensive and safe therapy; dissemination of stimulus or seizures from the target have been reported [ 31 , 32 ]. In fact, most trials assessing its effects on chronic or CRPS pain have few heterogeneous patients treated, and the conclusions are negative, inconsistent or inconclusive.
Besides that, the follow-up times were usually short, the parameters of stimulation and targets were heterogeneous, many of them were not randomized, and the different evaluation methods make difficult to compare results or properly put them together in a meta-analyses study. Therefore, these methods have level C or D of recommendation. The evidences to graduate PNS as grade C of recommendation in CRPS comes from a single prospective non-controlled series [ 33 , 34 ] and some case reports which have informed pain good relief when it was restricted to a major nerve division [ 35 , 36 ].
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Although function and atrophic changes are not affected, activity level and vasomotor improvement were reported. Although DRGS has been proposed as an efficient strategy to get pain relief in CRPS patients, the current evidences are still weak and based on few case reports and small uncontrolled studies to treat chronic pain or CRPS patients [ 37 - 42 ].
Van Buyten [ 42 ] has reported the results of DRGS of eight patients with successful trial stimulation from eleven CRPS patients that were enrolled in a large multicenter study to treat chronic pain from different etiologies. In addition, it had positives effects on mood, quality of life, mobility and several sympathetically signs. These facts could save energy, avoid displacement and necessity of electrodes replacement. Even though the grade of recommendation is not a consensus Grade B or C , SCS is the neuromodulation technique which has the best level of evidence as an effective intervention to treat refractory CRPS pain.
According to this, a Cochrane systematic review and three others papers in the medical literature have concluded for limited evidence in quality and quantity [ 21 , 29 , 43 , 44 ]. Although the risks of death or critical complications with SCS were uncommon and low, undesirable occurrences were frequent and costs were considered high.
In fact, these reviews have found a modest pain-relieving outcome with high rates of complications. He reasoned that it is hard to calculate due to the high variability in device cost, longevity, complications and necessity of revisions or replacement of devices components. Though many case series have reported positive effects of SCS, Kemler [ 24 - 26 ] has published the only high quality randomized controlled trial. Actually, it was reported in three papers that have assessed the six-month, two-year and fiveyear follow-up time. Actually, the majority conclusions in the major meta-analyses and systematic reviews about SCS effectiveness on CRPS pain treatment were supported by it.
In its final analyses, Kemler concluded that the pain-relieving effect decreased from device implantation to the third-year follow-up, when it was not significant. Assuming SCS is successful, an economic analysis demonstrated that it can be cost-effective and, even more economic than further treatments, in two years [ 26 ]. Despite of these critical analyses, this issue is far from consensus. Taylor [ 46 ] has considered SCS on CRPS pain treatment as grade A of recommendation though the studies included in his systematic review were almost the same which were cited above.
According to that, Poree [ 28 ] does not consider SCS as final therapy, but he proposed to ponder that precociously in early stages as traditional interventions have been shown unsuccessful.
http://lcdprojectormovies.com/the-best-mobile-phone-locate-software-android.php To date, there are few reports about CRPS patients treated with this technique though it seems to have significant effect on CRPS pain [ 47 - 50 ] and superior weighted responder rate than non-invasive techniques [ 51 ]. Even though MCS has high cost and higher complication rates as well as other invasive stimulation technics , at this time it is more commonly employed than DBS, since it is more easily carried out and it has a large spectrum of indications [ 52 ].
Currently, there is no high-quality randomized trial assessing MCS to treat CRPS patients, although Fontaine [ 53 ] assessed its effectiveness and side effects on chronic neuropathic pain approach in a systematic review. The most frequent complications reported were infections 5. Several authors have reported their lasting successful pain relief with DBS to treat either nociceptive or neuropathic chronic pain, though different targets, surgical procedures and stimulation techniques have been complicating a critical and comparative analysis [ 54 ].
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Generally speaking, periaqueductal gray PAG and periventricular gray PVG stimulation are recommended for the treatment of lasting nociceptive pain; whilst ventroposterolateral VPL , ventroposteromedial thalamic nucleous VPM or internal capsule IC stimulation are advocated for neuropathic pain [ 55 - 63 ]. The absence of randomized controlled trial and high quality meta-analysis studies also makes it difficult to get a better perception of DBS usefulness in CRPS pain treatment.
In addition, the cases included were very heterogeneous and the methods to assess pain and outcomes were not standardized [ 64 ]. Although neuromodulation is an emerging approach that seems to be safe and efficient to treat chronic pain, its use in CRPS patients is far from consensus. In recent years, trials using neuromodulation have been increasing fast in both quantity and quality, although the quality of evidences and recommendation are still weak.
In an overall attempt much of evidences come from case reports, retrospective case series or prospective studies with short follow-up and small number of patients.
In addition, many of them lack methodology quality in terms of randomization, blinding, controls and pain assessments. Can it be improved by unilateral or bilateral training? A kinematic motion analysis study. Archives of Physical Medicine and Rehabilitation , Platz T and Denzler P.