Not generally recommended as a diagnostic test for CRPS. See CRPS, diagnostic tests.
See NSAIDs (non-steroidal anti-inflammatory drugs); NSAIDs, GI symptoms & cardiovascular risk; NSAIDs, hypertension and renal function; & NSAIDs, specific drug list & adverse effects for general guidelines, as well as specific Sulindac (Clinoril®) listing for more information and references.
See specific entries in body part chapters in the DWC MTUS.See also CRPS, sympathectomy; CRPS, spinal cord stimulators (SCS); Implantable drug-delivery systems (IDDSs); Spinal cord stimulators (SCS).
Not recommended. Sympathetic therapy is considered investigational. The lack of published outcomes from well-designed clinical trials prohibits scientific conclusions concerning the health outcome effects of sympathetic therapy for the treatment of pain. Sympathetic therapy describes a type of electrical stimulation of the peripheral nerves that is designed to stimulate the sympathetic nervous system in an effort to "normalize" the autonomic nervous system and alleviate chronic pain. Unlike TENS (transcutaneous electrical nerve stimulation) or interferential electrical stimulation, sympathetic therapy is not designed to treat local pain, but is designed to induce a systemic effect on sympathetically induced pain. The Dynatron STS device and a companion home device, Dynatron STS Rx, are devices that deliver sympathetic therapy. These devices received U.S. Food and Drug Administration (FDA) clearance in March 2001 through a 510(k) process. The FDA-labeled indication is as follows: "Electrical stimulation delivered by the Dynatron STS and Dynatron STS Rx is indicated for providing symptomatic relief of chronic intractable pain and/or management of post-traumatic or post-surgical pain." (Werners, 1999) (Washington State, 2002) (BlueCross BlueShield, 2005) (Aetna, 2005) See also Interferential therapy and relevant DWC MTUS body chapters.
Sympathetically independent pain (SIP)
See Sympathetically maintained pain (SMP).
Sympathetically maintained pain (SMP)
Definition: Sympathetically maintained pain (SMP) is pain that is maintained by sympathetic efferent innervation or by circulating catecholamines. (Stanton-Hicks, 1995) In more chronic stages, SMP may develop into sympathetically independent pain (SIP) or there may be mixed elements. (Ribbers, 2003) SMP and SIP may also be seen in almost any type of neuropathic pain disorder. Therefore, pain relief may be found after sympatholysis in multiple conditions in addition to CRPS, and may be a reflection of response to sympathetic activity found in other sympathetically maintained pain conditions. (Stanton-Hicks, 2004) See CRPS, diagnostic criteria; CRPS, medications; CRPS, sympathetic and epidural blocks; & Regional sympathetic blocks.
Recommended as an exercise-therapy option for arthritis, and for fibromyalgia when requested by highly motivated patients. Exercise therapy such as strengthening, stretching and aerobic programs, have been shown to be effective for arthritic pain. Tai Chi is a form of exercise that is regularly practiced in China to improve overall health and well-being. It is usually preformed in a group but is also practiced individually at one’s leisure. The fact that Tai Chi is inexpensive, convenient, and enjoyable and conveys other psychological and social benefits supports the use this type of intervention for pain conditions such as arthritis. It is important to note that the results reported in this systematic review are indicative of the effect of Tai Chi versus minimal intervention (usual health care or health education) or wait list control, but establishing the specific effects of Tai Chi would require a placebo-controlled trial, which has not yet been undertaken. (Hall, 2009) Tai chi may be a helpful intervention for patients with fibromyalgia. (Wang, 2010) Outcomes from this therapy are very dependent on the highly motivated patient. See Physical medicine treatment for recommended number of visits if exercise training is prescribed.
See Pentazocine (Talwin/Talwin NX).
Recommended only as second-line therapy for patients who develop intolerable adverse effects with first-line opioids. Three large RCTs concluded that tapentadol was efficacious and provided efficacy that was similar to oxycodone for the management of chronic osteoarthritis knee and low back pain, with a superior gastrointestinal tolerability profile and fewer treatment discontinuations. (Afilalo, 2010) (Buynak, 2010) (Lange, 2010) Tapentadol is a centrally acting oral analgesic. It has two mechanisms of action, combining mu-opioid receptor agonism and norepinephrine reuptake inhibition. (Johnson, 2008) Nucynta™ (tapentadol) was made a Schedule II controlled substance. Nucynta™ may be abused by crushing, chewing, snorting or injecting the product. These practices pose a significant risk to the abuser that could result in overdose and death. (FDA, 2009) Nucynta has the same pain-relieving benefits of OxyIR, as well as the same risks that come with any opioid, but shows a significant improvement in gastrointestinal tolerability compared with oxycodone; if patients on OxyIR complain of constipation, nausea, and/or vomiting, Nucynta may be considered as a second-line choice. (Daniels, 2009) (Daniels2, 2009) (Hale, 2009) (Hartrick, 2009) (Stegmann, 2008) In one study, gastrointestinal adverse events led to discontinuation in 9% of the tapentadol group versus 22% of the oxycodone group. (Wild, 2010)
Telomerase activators (TA-65)
Appropriate only in a research setting until higher quality studies are available. Telomeres are the ends protecting each chromosome that become progressively shorter each time the cell divides until the cell can no longer divide, potentially resulting various conditions associated with old age, including pain, cancer, etc. Telomerase is an enzyme used as a template when it elongates telomeres, which are shortened after each replication cycle. Chronic pain/high stress groups have significantly shorter telomere length. (Sibille, 2012) Most human cells lack sufficient telomerase to maintain telomeres, hence these genetic elements shorten with time and stress, contributing to aging and disease. A natural product-derived telomerase activator can moderately activate telomerase. (Harley, 2011) Shortening of leukocyte telomeres, the extreme ends of chromosomal DNA, is associated with risks for mortality, and may be a marker of biological aging, according to this study. (Honig, 2012)
Not recommended as a primary treatment modality, but a one-month home-based TENS trial may be considered as a noninvasive conservative option, if used as an adjunct to a program of evidence-based functional restoration, including reductions in medication use, for the conditions described below. While TENS may reflect the long-standing accepted standard of care within many medical communities, the results of studies are inconclusive; the published trials do not provide information on the stimulation parameters which are most likely to provide optimum pain relief, nor do they answer questions about long-term effectiveness. (Carroll-Cochrane, 2001) Several published evidence-based assessments of transcutaneous electrical nerve stimulation (TENS) have found that evidence is lacking concerning effectiveness. One problem with current studies is that many only evaluated single-dose treatment, which may not reflect the use of this modality in a clinical setting. Other problems include statistical methodology, small sample size, influence of placebo effect, and difficulty comparing the different outcomes that were measured.
Recommendations by types of pain: A home-based treatment trial of one month may be appropriate for neuropathic pain and CRPS II (conditions that have limited published evidence for the use of TENS as noted below), and for CRPS I (with basically no literature to support use).
Neuropathic pain: Some evidence (Chong, 2003), including diabetic neuropathy (Spruce, 2002) and post-herpetic neuralgia. (Niv, 2005)
Phantom limb pain and CRPS II: Some evidence to support use. (Finsen, 1988) (Lundeberg, 1985)
Spasticity: TENS may be a supplement to medical treatment in the management of spasticity in spinal cord injury. (Aydin, 2005)
Multiple sclerosis (MS): While TENS does not appear to be effective in reducing spasticity in MS patients it may be useful in treating MS patients with pain and muscle spasm. (Miller, 2007)
See also DWC MTUS chapters on specific body parts.
How it works: TENS consists of an electrical pulse generator connected to skin-surface electrodes that apply stimulation to peripheral nerves at well-tolerated frequencies. Electrodes can either be placed at the site of pain or other locations, using a trial and error methodology. A TENS unit can be varied by amplitude, pulse width (duration) and pulse rate (frequency). The most common applications include (1) high frequency or conventional TENS (40-150 Hz, with a short duration of up to 50 microseconds) and (2) low frequency or acupuncture-like TENS (1-4 Hz at a high stimulus intensity). Other modes of TENS include: (1) brief-intense TENS (>80 Hz); (2) burst TENS (bursts at less than 10 Hz) at high frequency; and (3) modulation TENS. The difference between clinical effectiveness of the modalities has not been well defined. (Koke, 2004) TENS should be differentiated from other types of electrical stimulators. See Electrical stimulators (E-stim) for a list of alternatives.
Recent studies: A meta-analysis concluded that there was a significant decrease in pain when electrical nerve stimulation (ENS) of most types was applied to any anatomic location of chronic musculoskeletal pain (back, knee, hip, neck) for any length of treatment. Of the 38 studies used in the analysis, 35 favored ENS over placebo. All locations of pain were included based on the rationale that “mechanism, rather than anatomic location of pain, is likely to be a critical factor for therapy.” The overall design of this study used questionable methodology and the results require further evaluation before application to specific clinical practice. (Johnson, 2007) (Novak, 2007) (Furlan, 2007) Although electrotherapeutic modalities are frequently used in the management of CLBP, few studies were found to support their use. Most studies on TENS can be considered of relatively poor methodological quality. TENS does not appear to have an impact on perceived disability or long-term pain. High frequency TENS appears to be more effective on pain intensity when compared with low frequency, but this has to be confirmed in future comparative trials. It is also not known if adding TENS to an evidence-based intervention, such as exercise, improves even more outcomes, but studies assessing the interactions between exercise and TENS found no cumulative impact. (Poitras, 2008) A recent meta-analysis concluded that the evidence from the small number of placebo-controlled trials does not support the use of TENS in the routine management of chronic LBP. There was conflicting evidence about whether TENS was beneficial in reducing back pain intensity and consistent evidence that it did not improve back-specific functional status. There was moderate evidence that work status and the use of medical services did not change with treatment. Patients treated with acupuncture-like TENS responded similarly to those treated with conventional TENS. (Khadilkar-Cochrane, 2008) An evidence-based review concluded that TENS is not recommended for use in treating chronic low-back pain (level A, 2 class 1 studies) but adds that TENS should be considered to treat diabetic neuropathy (level B, 2 class 2 studies). In the highest-quality studies of chronic low back pain, there was no benefit of TENS compared to sham or placebo TENS. In diabetic polyneuropathy, some studies showed slight benefit. The authors also point out that TENS has had a long-standing role in pain management, is easy to handle, has a favorable benefit-to-risk ratio, and can be discontinued easily if it is not efficacious. (Dubinsky, 2010)
TENS, post operative pain (transcutaneous electrical nerve stimulation)
Recommended as a treatment option for acute post-operative pain in the first 30 days post-surgery. Transcutaneous electrical nerve stimulation (TENS) appears to be most effective for mild to moderate thoracotomy pain. (Solak, 2007) (Erdogan, 2005). It has been shown to be of lesser effect, or not at all for other orthopedic surgical procedures. (Breit, 2004) (Rosenquist 2003) The proposed necessity of the unit should be documented upon request. Rental would be preferred over purchase during this 30-day period.
Testosterone replacement for hypogonadism (related to opioids)
Recommended in limited circumstances for patients taking high-dose long-term opioids with documented low testosterone levels. Hypogonadism has been noted in patients receiving intrathecal opioids and long-term high dose opioids. Routine testing of testosterone levels in men taking opioids is not recommended; however, an endocrine evaluation and/or testosterone levels should be considered in men who are taking long term, high dose oral opioids or intrathecal opioids and who exhibit symptoms or signs of hypogonadism, such as gynecomastia. If needed, testosterone replacement should be done by a physician with special knowledge in this field given the potential side effects such as hepatomas. There are multiple delivery mechanisms for testosterone. Hypogonadism secondary to opioids appears to be central, although the exact mechanism has not been determined. The evidence on testosterone levels in long-term opioid users is not randomized or double-blinded, but there are studies that show that there is an increased incidence of hypogonadism in people taking opioids, either intrathecal or oral. There is also a body of literature showing that improvement in strength and other function in those who are testosterone deficient who receive replacement. (Nakazawa, 2006) (Page, 2005) (Rajagopal, 2004) This appears to be more pronounced in patients taking oral opioids than in patients receiving intrathecal opioids, and this difference seems to be related to differences in absorption. Hypogonadism secondary to opioids appears to be central, although the exact mechanism has not been determined. (Abs, 2000) (Roberts, 2002) (Roberts, 2000) The odds of being hypogonadal on long-acting opioids may be 4-5 times higher than the odds on a short-acting equipotent dose. (Rubinstein, 2012) Etiology of decreased sexual function, a symptom of hypogonadism, is confounded by several factors including the following: (1) The role of chronic pain itself on sexual function; (2) The natural occurrence of decreased testosterone that occurs with aging; (3) The documented side effect of decreased sexual function that is common with other medications used to treat pain (SSRIs, tricyclic antidepressants, and certain anti-epilepsy drugs); & (4) The role of comorbid conditions such as diabetes, hypertension, and vascular disease in erectile dysfunction. There is little information in peer-reviewed literature as to how to treat opioid induced androgen deficiency.
Long-term safety data of testosterone replacement (overall): Not available.
Cardiovascular risk: There have been no large randomized controlled trials to evaluate the cardiovascular risk associated with long-term testosterone use, although current studies weakly support that there is no association with important cardiovascular effects. (Haddad 2007)
Osteoporosis: The extent to which testosterone can prevent and treat osteoporosis remains unclear. (Tracz 2006) (Isidori, 2005)
Sexual function: Current trials of testosterone replacement in patients with documented low testosterone levels have shown a moderate nonsignificant and inconsistent effect of testosterone on erectile function, a large effect on libido, and no significant effect on overall sexual satisfaction. (Bolona, 2007) (Isidori, 2005)
The one study (sponsored by the drug company) that has evaluated the use of testosterone replacement in patients with opioid-induced androgen deficiency, measured morning serum free testosterone levels and PSA prior to replacement. This study did not include patients taking antidepressants. (Daniell, 2006)
Not recommended for the treatment of chronic pain. See Medical foods.
Thermography (infrared stress thermography)
Not recommended. There is insufficient evidence to support the routine use of thermography for diagnosis of CRPS. Thermography is a non-invasive imaging technique, which is intended to measure temperature distribution of various organs and tissues. The infrared radiation from the tissue reveals temperature variations by producing brightly colored patterns on a liquid crystal display. Interpretation of the color patterns is claimed by some to assist in the diagnosis of many disorders such as breast cancer, Reynaud’s phenomenon, digital artery vasospasm in hand-arm vibration syndrome, impaired spermatogenesis in infertile men, degree of burns, deep vein thrombosis, gastric cancer, tear-film layer stability in dry-eye syndrome, Frey's syndrome, headaches, low-back pain, reflex sympathetic dystrophy, and vertebral subluxation. There is insufficient evidence in the peer-reviewed published literature to reach conclusions concerning the effects of thermography on health outcomes for any indication. (Krumova, 2008) (Schurmann, 2007) (Gradl, 2003) See CRPS, diagnostic tests.