ID# 1904124 Peripheral Nerve Stimulation in the Treatment of Chronic Pain: A Historical and Technical Review

Dorsal column stimulation (DCS) was used in the treatment of chronic intractable pain in 51 patients. Twenty-five of the patients had back and leg pain secondary to the treatment of intervertebral disc disease; 11 had postoperative pain after general or thoracic surgical procedures. The remainder suffered pain related to multiple sclerosis, spinal cord injury, carcinoma, and peripheral vascular disease. Pain had been present for a mean of 24 months. Thirty-seven patients underwent DCS electrode placement by open laminectomy, and 11 had percutaneous epidural DCS electrode placement. Three patients first underwent epidural DCS electrode implantation and subsequently had DCS electrode implantation by laminectomy. No major complications were noted, although multiple lesser complications required 33 additional operative procedures for correction. Follow-up periods ranged from 12 to 67 months, with a mean of 38 months. Immediately after implantation. 47% of the patients reported that they had essentially complete pain relief, but 3 years later this had decreased to 8%. No patient followed for 4 years or longer reported complete pain relief. Thirty-three per cent of the patients discontinued the regular use of narcotics for pain relief after DCS electrode implantation. Unfortunately, only 16% were able to return to gainful employment or full physical activity after DCS. Based on these data and a review of the literature, the following conclusions are made: (a) assessment of success in the treatment of chronic pain is strongly dependent on the criteria used for patient evaluation: (b) with the criteria of this report, DCS is a relatively ineffective treatment for chronic pain; (c) epidural percutaneous DCS systems are no more effective than are those placed by laminectomy, and, because of technical problems with epidural systems (mainly lead breakage and migration), the latter may actually be less effective; and (d) at present DCS seems to play a minor role in the treatment of chronic intractable pain.

Management of Adolescent Chronic Pelvic Pain from Endometriosis: A Pain Center Perspective

The association between vitamin D deficiency or insufficiency and pain in the musculoskeletal system, especially in the neck and/or back regions, and/or muscle spasm is not well studied. The results of the limited studies have been mixed. The goal of this report is to examine the association between vitamin D deficiency and insufficiency and chronic neck and back pain and muscle spasm and the role of correction of vitamin D deficiency and insufficiency in the treatment of chronic pain and muscle spasm, especially in the neck and back regions. This case series reviewed medical records to identify patients with chronic pain (lasting from 6 months to 1 year) in the neck and back regions that improved significantly through the correction of the vitamin D deficiency or insufficiency. Patients were referred to the spine clinic of a tertiary hospital in a major metropolitan area in the Northwest by their primary care physicians after physical therapy and after first-tier pain medications, including nonsteroidal anti-inflammatory drugs, had failed. Some of the patients had epidural steroid injections without significant relief. The blood vitamin D level was tested at the clinical laboratory, and patients were given 50,000 IU of oral vitamin D once a week for 12 weeks. The main outcome measures were patient self-reported visual analog scale score and degree of muscle spasm. The 4 patients included in this series all had more than 70% improvement in their symptoms after taking 50,000 IU of vitamin D once a week for 12 weeks. Vitamin D deficiency and insufficiency can cause or worsen neck and back pain and muscle spasm. The correction of vitamin D deficiency and insufficiency plays an important role in the treatment of chronic neck and back pain and muscle spasm among patients having concurrent vitamin D deficiency and insufficiency because it can be prevented and treated easily.Given the high health care expenditure on the treatment of chronic neck and back pain, prompt and accurate diagnosis and treatment of vitamin D deficiency and insufficiency not only increase the quality of care but also reduce the cost.

BackgroundThe use of opioid medications as treatment for chronic non-cancer pain remains controversial. Little information is currently available regarding healthcare providers' attitudes and beliefs about this practice among older adults. This study aimed to describe primary care providers' experiences and attitudes towards, as well as perceived barriers and facilitators to prescribing opioids as a treatment for chronic pain among older adults.MethodsSix focus groups were conducted with a total of 23 physicians and three nurse practitioners from two academically affiliated primary care practices and three community health centers located in New York City. Focus groups were audiotape recorded and transcribed. The data were analyzed using directed content analysis; NVivo software was used to assist in the quantification of identified themes.ResultsMost participants (96%) employed opioids as therapy for some of their older patients with chronic pain, although not as first-line therapy. Providers cited multiple barriers, including fear of causing harm, the subjectivity of pain, lack of education, problems converting between opioids, and stigma. New barriers included patient/family member reluctance to try an opioid and concerns about opioid abuse by family members/caregivers. Studies confirming treatment benefit, validated tools for assessing risk and/or dosing for comorbidities, improved conversion methods, patient education, and peer support could facilitate opioid prescribing. Participants voiced greater comfort using opioids in the setting of delivering palliative or hospice care versus care of patients with chronic pain, and expressed substantial frustration managing chronic pain.ConclusionsProviders perceive multiple barriers to prescribing opioids to older adults with chronic pain, and use these medications cautiously. Establishing the long-term safety and efficacy of these medications, generating improved prescribing methods, and implementing provider and patient educational interventions could help to improve the management of chronic pain in later life.

Chronic pain occurs in 45-85% of the geriatric population and the need to treat chronic pain is growing substantially. Unfortunately, treatment for chronic pain is not always correctly targeted, which leads to a reduced quality of life, with decreased socialization, depression, sleep disturbances, cognitive impairment, disability and malnutrition. Considering these consequences, healthcare professionals should aim at improving the diagnosis and treatment of chronic pain in older persons. One of the most important limitations in achieving successful pain management is that older people are not aware that pain management options exist or medications for pain, such as opioids, have associated benefits and adverse effects. Importantly, opioids do not induce any organ failure and if adequately used at the right dosage may only present some predictable and preventable adverse effects. Treating and controlling chronic pain is essential in elderly patients in order to maintain a good quality of life and an active role in both the family and society. To date there are only a few randomized clinical trials testing opioid therapy in elderly patients, and the aim of the present review is to highlight the efficacy and tolerability of opioid use through a literature search strategy in elderly people with chronic non-cancer pain.

Transdermal buprenorphine in the treatment of chronic pain: Resultsof a phase III, multicenter, randomized, double-blind, placebo-controlled study

BackgroundIn children with chronic pain, interdisciplinary outpatient and intensive inpatient treatment has been shown to improve pain intensity and disability. However, there are few systematic comparisons of outcomes of the two treatments. The present naturalistic study aimed to compare the clinical presentation and achieved changes at return in three outcome domains (pain intensity, disability, school absence) between a) outpatients vs. inpatients and b) patients who declined intensive inpatient treatment and completed outpatient treatment instead (decliners) vs. those who completed inpatient treatment (completers).MethodsThe study compared treatment outcomes between n = 992 outpatients vs. n = 320 inpatients (Analysis A) who were treated at a tertiary treatment centre and returned for a return visit within a one-year interval. In Analysis B, treatment outcomes were compared between n = 67 decliners vs. n = 309 completers of inpatient treatment. The three outcome domains were compared by calculating standardized change scores and clinically significant changes.ResultsIn analysis A, outpatients and inpatients reported comparably low levels of pain intensity (NRS 0–10; mean = 4, SD = 2.7) and disability (Paediatric Pain Disability Index (PPDI: 12–60; mean = 24; SD = 10) at the return visit. Compared to outpatients, more inpatients achieved clinically significant changes in pain intensity (52% vs. 45%) and disability (46% vs. 31%). There were also significantly greater changes in disability in the inpatient group (change score outpatients = 1.0; change score inpatients = 1.4; F(1,1138) = 12.6, p = .011). School absence was substantially reduced, with approximately 80% in each group attending school regularly. Analysis B showed that even though inpatient decliners achieved improvements in the outcome domains, they reported greater disability at the return visit (PPDI mean decliners = 27, SD = 9.9; PPDI mean completers = 24, SD = 10) because they had achieved fewer changes in disability (change score decliners = 0.9; change score completers = 1.4; F(1.334) = 5.7, p = .017). In addition, less decliners than completers achieved clinically significant changes in disability (25% vs. 47%).ConclusionsInpatient and outpatient treatments are able to elicit substantial changes in pain intensity, disability and school absence. The results highlight the necessity of intensive inpatient pain treatment for highly affected children, as children who declined inpatient treatment and were treated as outpatients did less well.

Treatment of chronic pain with millimetre wave therapy (MWT) in patients with diffuse connective tissue diseases: a pilot case series study

Highly selective N-type voltage-gated calcium (CaV) channel inhibitors from cone snail venom (the ω-conotoxins) have emerged as a new class of therapeutics for the treatment of chronic and neuropathic pain. Earlier in 2005, Prialt (Elan) or synthetic ω-conotoxin MVIIA, was the first ω-conotoxin to be approved by Food and Drug Administration for human use. This review compares the action of three ω-conotoxins, GVIA, MVIIA and CVID, describing their structure-activity relationships and potential as leads for the design of improved N-type therapeutics that are more useful in the treatment of chronic pain.

Background and aimKetamine is a drug used for the induction and maintenance of general anesthesia, for the treatment of postoperative and posttraumatic acute pain, and more recently, for the reduction of postoperative opioid requirements. The main mechanism of action of ketamine is the antagonization of N-methyl-D-aspartate (NMDA) receptors that are associated with central sensitization. In the pathogenesis of chronic pain and particularly in neuropathic pain, an important role is played by the activation of NMDA receptors. Although ketamine is indicated and used for the treatment of chronic cancer pain as an adjuvant to opioids, there are few clinical studies that clearly demonstrate the effectiveness of ketamine in this type of pain.The aim of this study is to analyze evidence-based clinical data on the effectiveness and safety of ketamine administration in the treatment of chronic neoplastic pain, and to summarize the evidence-based recommendations for the use of ketamine in the treatment of chronic cancer pain.MethodWe reviewed the literature from the electronic databases of MEDLINE, COCHRANE, PUBMED, MEDSCAPE (1998–2014), as well as chapters of specialized books (palliative care, pain management, anesthesia).ResultsA number of studies support the effectiveness of ketamine in the treatment of chronic cancer pain, one study does not evidence clear clinical benefits for the use of ketamine, and some studies included too few patients to be conclusive.ConclusionsKetamine represents an option for neoplasic pain that no longer responds to conventional opioid treatment, but this drug should be used with caution, and the development of potential side effects should be carefully monitored.

Chronic pain is a multifactorial condition that is afflicting populations worldwide causing an increasing economic, physical, mental, and emotional burden. Treatments range from medications to interventional procedures to complementary and alternative medicine (CAM), such as acupuncture. This review aims to discuss the use of acupuncture in the treatment of chronic pain, proposed mechanisms, indications, and efficacy for various chronic pain conditions. Evidence is varied on the efficacy and quality of data on the use of acupuncture in the treatment of chronic pain. Recent studies have demonstrated promising results in the support of acupuncture for the use in the treatment of cancer, neck, and back pain, functional dyspepsia, and various chronic abdominal pain syndromes. Acupuncture, deemed well-tolerated and safe to use, has been increasingly studied and is regarded as effective in clinical practice, but its efficacy is limited by the lack of well-conducted, high-quality clinical trials, lower quality evidence, and conflicting study results. Additionally, the exact analgesic mechanism of acupuncture remains to be fully elucidated. Increasing evidence supports the role of acupuncture as therapy in the treatment of cancer, neck, and back pain and functional dyspepsia. Further rigorous studies are needed to fully assess the use of acupuncture in various chronic pain conditions, determine its indications, and optimal treatment schedule. Overall, future studies could benefit from better designed experimental studies, larger groups, and more objectives ways to measure pain reduction and symptom improvement.

Recent advances in the treatment of chronic pain and substance use disorders.

Peripheral nerve stimulating devices were implanted for pain control in 33 patients with a variety of disabling chronic pain conditions, which had persisted despite usual medical and surgical therapy. The implants were placed on major nerves innervating the area of the patient's pain. Records were obtained of each patient's stated relief from pain produced by nerve stimulation, along with assessments of narcotic withdrawal, ability to return to work, sleep pattern, and relief from depression. Based on these five criteria 17 patients were judged to be treatment failures, while eight patients had excellent results, and seven had intermediate results. Twelve of the failures were in patients with either low back pain with sciatica, or pain from metastatic disease. The most dramatic successes occurred in patients with peripheral nerve trauma. The incidence of complications has been low, and two patients have used the stimulator for 5 years without adverse effects. Techniques of peripheral stimulator implantation, possible mechanisms of action, and conclusions regarding peripheral nerve stimulation in the treatment of chronic pain are discussed.

The number of peripheral nerve stimulation (PNS) indications, targets, and devices is expanding, yet the development of the technology has been slow because many devices used for PNS do not have formal regulatory approval. Manufacturers have not sought Food and Drug Administration (FDA) approval for PNS devices because of a perceived lack of interest amongst practitioners and patients. Without FDA approval, companies cannot invest in marketing to educate the implanters and the patients about the benefits of PNS in the treatment of chronic pain. Violation of this has resulted in governmental investigation and prosecution. Most of the PNS devices currently used to treat chronic pain are FDA approved for epidural spinal cord stimulation. Many of the complications seen in PNS surgery can be attributed to the lack of purpose-built hardware with FDA approval. Despite the lack of regulatory approval, there are insurance companies that approve PNS procedures when deemed medically necessary. As the targets and indications for PNS continue to expand, there will be an even greater need for customized technological solutions. It is up to the medical device industry to invest in the design and marketing of PNS technology and seek out FDA approval. Market forces will continue to push PNS into the mainstream and physicians will increasingly have the choice to implant devices specifically designed and approved to treat chronic peripheral nerve pain.

Sir, Opioids have been used for decades and continue to be used to treat severe, acute, chronic non-cancer and cancer pain.1,2 They work mainly by inhibiting spinal cord neuronal transduction and the ascending pain signals at midbrain nuclei, and through the modulation of limbic system pain perception.3 The main opioids receptors are mu and kappa receptors.1–3 The use of opioids can be challenging and not without severe or life-threatening side-effects.1,2 The World Health Organization (WHO) has recommended the adoption of a three-step analgesic ladder to meet the therapeutic challenges of administering opioids and to reduce the incidence of these side-effects. This can be achieved by starting with non-opioid analgesics followed by weak opioids with adjuvants, reserving strong opioids for cases of severe pain.2,3 When we escalate the opioid dose without getting the expected clinical response, then we may face the dilemma of tolerance, which can be defined as a decrease in pharmacologic response following repeated or prolonged drug administration. In the case of opioids, patients may experience opioid-induced hyperalgesia (OIH), which is a state of nociceptive sensitisation caused by exposure to opioids that leads to an increased response to a stimulus which is normally painful.1–4 In our practice, it is not uncommon to face this dilemma, especially during the management of patients who require long-term pain treatment with opioids.1,4 Although tolerance is faced frequently, we should not fail to recognise OIH by classifying all cases of poor response to escalating opioids as tolerance. In fact, much of the literature refers to the difficulty in differentiation between these two conditions.1,4 All patients with OIH have some sort of tolerance but the reverse is not true.1,2 Opioid-induced tolerance is rarely a limiting factor during opioid therapy in clinical practice and should not delay the start of treatment or dose escalation in patients with chronic pain.3 We should not refer to every pain-worsening during the course of therapy, as tolerance unless a detailed clinical evaluation fails to show any clear alternative cause.1,4 In OIH, the pain can become more widespread, occur in areas beyond the original pain location, and may be associated with allodynia. It occurs with various routes of administration, happening more frequently in intermittent boluses with cessation in between, than with continuous infusion.1,4 OIH is more evident with prolonged use of opioids. However, there is evidence of patients developing hyperalgesia after only short-term intraoperative opioids exposure.1,4,6 The degree or gradation of opioid tolerance is generally related to duration of exposure, daily dose requirement, and receptor association/disassociation kinetics. The mechanism of opioid-induced tolerance may include, among other things, the desensitisation to, or internalisation of opioid receptors. This is marked by a decrease in opioid binding sites that are available to provide pain relief.1–3 Another cause of tolerance is an increase in spinal cord concentrations of dynorphin, which promotes abnormal pain and acts to reduce the antinociceptive efficacy of spinal opioids.2,3 The sensitisation of N-methyl-D-aspartate (NMDA)-sensitive glutamate receptors may play a role in opioid-induced tolerance. This is evident as NMDA-antagonists like ketamine can attenuate tolerance development and decreases in dosage, which may delay the onset of tolerance.5 The mechanism of OIH is complex and not always clear. Usually more than one mechanism is involved.4 In OIH, five possible mechanisms are involved, including activation of the central glutaminergic system; an increase in spinal dynorphins; activation of descending facilitation due to neuroplastic changes in rostroventral medulla; genetic mechanisms, and decreased reuptake of excitatory neurotransmitters and an enhanced nociceptive response. Among these five mechanisms proposed to explain OIH, the activation of NMDA-sensitive glutamate receptors is the most common possibility.1,4 Prostaglandins and cytokines might also be relevant to the development of OIH.2 As a rule, when it comes to tolerance, the increase in pain should be overcome by increasing the dose, thus providing a mode of easy diagnosis.2,3 While the diagnosis of OIH might not be straightforward, in general, if the opioids dose-reduction results in an improvement in pain control, OIH is the most likely cause. If the pain worsens, then opioid tolerance is the most likely cause.1,3,4 Quantitative sensory testing (QST), which is used to assess neurological function in chronic pain patients, can also be helpful in predicting OIH. It is performed before the initiation of opioid treatment and then repeated at certain intervals. Any changes in pain threshold upon QST can suggest OIH if other causes have been excluded.1,4 Tolerance can be treated by increasing the opioid dose. The addition of adjuvant medications like nonsteroidal anti-inflammatory drugs (NSAIDs), tricyclic antidepressant (TCA), pregabalin and others may be effective in reduction of the required opioids and delay in occurrence of tolerance.2,3 Ketamine has a dual action here as it can be used as an analgesic in low doses in addition to the NMDA antagonist effect, which can attenuate receptor sensitisation and hence, the development of tolerance.3,5 OIH treatment is much more complex and requires a specific strategy which may vary from one patient to another.1,4 This can be difficult, time-consuming ,and even impractical.1 Practically speaking, opioid reduction might induce withdrawal symptoms, which can include an increase in pain.1,4 That increase in pain will mask the clinical picture and make the differentiation more difficult.2,4 The long course of weaning which is required for those patients can cause frustration and they may give up and stop the process. This type of treatment may also require special institutes.1 Several drugs have been used to reduce the possibility of developing OIH, especially when opioid dose-reduction is not accepted or tolerated by the patient.4,6 Evidence showed that low-dose ketamine, an NMDA-receptor blocker, can modulate OIH.1,4–6 Methadone, which is a weak NMDA-receptor blocker and buprenorphine, which is a partial opioid mu agonist, can play roles in the treatment of chronic pain and OIH.1,6 Buprenorphine is an opioid partial agonist with a maximal effect which is less than that of full agonists. Buprenorphine is efficacious for longer-term opioid maintenance with a lower risk of abuse, addiction, and side effects as compared to full opioid agonists. Possible antihyperalgesics mechanisms include kappa-receptor antagonist properties and voltage-gated sodium channels blockade effects. It is an effective opioid detoxification agent with an equivalent or even better effect than methadone. Formulations for opioid detoxification treatment are in the form of sublingual tablets as they have very poor bioavailability. Transdermal patches are also available in Europe and North America for treatment of chronic pain.1,6 Other approaches may include adding NSAIDs (especially COX-2 inhibitors) as an adjuvant which may provide opioid-sparing effects in addition to modulating sensitised receptors by blocking prostaglandins.6 Anti-epileptic therapy (gabapentin or pregabalin) and α-2 receptor agonists (clonidine) can also attenuate chronic pain and reduce OIH.1,4,6 Opioid rotation is another strategy that can be used to overcome OIH.6 Finally, we can conclude that although opioids are widely used in the treatment of pain, especially chronic pain, they cannot be free of side-effects, including serious ones. OIH is one of these side-effects which may contribute to patient discomfort and carry harmful consequences if they are not diagnosed and treated. It is not uncommon to misdiagnose OIH as opioid-induced tolerance, although the treatment modalities may be different. Adding analgesic adjuvants like ketamine, COX-2 inhibitors, or gabapentinoids can reduce the required dose of opioids and attenuate both OIH and tolerance.