Novel Therapies for Centralized Pain: a Brief Review.

PURPOSE OF REVIEW: Centralized pain presents a complex pathology that many classic pharmacological agents for pain have not been able to sufficiently treat. To date, there are no clear guidelines for preferred treatment methods or comprehensive protocol that addresses confounding factors in this population. We sought to summarize the current field of knowledge around centrally mediated pain and to understand promising novel therapies. RECENT FINDINGS: Many treatments currently used address not only the centralized pain phenotypem but the impact of central sensitization and the common comorbidities that reside within this population. Some novel therapies with promising evidence include the following: low-dose naltrexone, IV ketamine, acupuncture, aerobic activity, and laser therapy. Non-interventional treatment options include aerobic exercise, cognitive-behavioral therapy, mind-body therapies, virtual reality, and patient education on disease expectations. Much of the literature further emphasizes the importance of patient-level predictors, including factors like pain catastrophizing and social history, on treatment compliance and reported pain relief. We found that there are many potential treatment options for patients with centralized pain, particularly those that can be used as adjunct or combination therapies. The introduction of new approaches should occur in a carefully controlled, titrated manner to avoid exacerbation of pain symptoms. This is successfully conducted through patient-physician communication as this is a highly complex and personalized pain category. Our examination shows that while physicians have many options with proven success, there is a need for studies with longitudinal and larger patient populations to better articulate treatment guidelines.

Intravenous Ketamine for Cancer Pain Management, Including Flares During the COVID-19 Pandemic: A Retrospective Study.

OBJECTIVES: Cancer-related neuropathic pain (CNP) affects an increasing proportion of cancer patients, given improved survival, but it remains difficult to treat. There are no studies on an extended intravenous ketamine protocol and its synergies with common neuropathy treatments to treat CNP. This study aims to 1) evaluate the safety and effectiveness of an intravenous ketamine protocol to treat refractory CNP and 2) uncover synergies between ketamine and common neuropathy treatments. METHODS: This is a single-center, retrospective review of 57 patients and 192 infusions, with prospective follow-up on 14 enrolled patients during the coronavirus disease 2019 (COVID-19) pandemic. RESULTS: The etiologies of CNP were as follows: 13 from tumor compression, 25 with chemotherapy-induced peripheral neuropathy, 13 from surgery, and 6 from radiation therapy. Overall, 42 of 57 patients (73.7%) were responders, and 71.8% of responders received >3 weeks of pain relief on their last infusion. Analysis of adjuvant treatments revealed that the combination of serotonin-norepinephrine reuptake inhibitors and ketamine resulted in an increase in responders compared with nonresponders (P < 0.01). Adverse events occurred in 32 of 192 infusions (16.7%). All side effects self-resolved or resolved with intervention per the adverse events protocol. During the pandemic, all 14 currently enrolled patients did not receive ketamine infusions. Thirteen of the 14 patients returned to baseline pain, with 61.5% increasing medications. All experienced worsened function, mobility, mood, or anorexia. CONCLUSION: Intravenous ketamine may be a safe and effective adjuvant treatment for CNP, especially with serotonin-norepinephrine reuptake inhibitors. Larger, prospective studies are warranted and should explore parameters to help prognosticate response to ketamine infusions.

Flavonoids in the Treatment of Neuropathic Pain.

PURPOSE OF REVIEW: Chronic pain continues to present a large burden to the US healthcare system. Neuropathic pain, a common class of chronic pain, remains particularly difficult to treat despite extensive research efforts. Current pharmacologic regimens exert limited efficacy and wide, potentially dangerous side effect profiles. This review provides a comprehensive, preclinical evaluation of the literature regarding the role of flavonoids in the treatment of neuropathic pain. RECENT FINDINGS: Flavonoids are naturally occurring compounds, found in plants and various dietary sources, which may have potential benefit in neuropathic pain. Numerous animal-model studies have demonstrated this benefit, including reversal of hyperalgesia and allodynia. Flavonoids have also exhibited an anti-inflammatory effect relevant to neuropathic pain, as evidenced by the reduction in multiple pro-inflammatory mediators, such as TNF-α, NF-κB, IL-1ß, and IL-6. Flavonoids represent a potentially new treatment modality for neuropathic pain in preclinical models, though human clinical evidence is yet to be explored at this time.

Tapentadol, Buprenorphine, and Levorphanol for the Treatment of Neuropathic Pain: a Systematic Review.

PURPOSE OF REVIEW: The objective of this systematic review is to present the available evidence for the utilization of the atypical opioids tapentadol, buprenorphine, and levorphanol for the treatment of neuropathic pain. RECENT FINDINGS: In total, 1619 articles were retrieved of which 10 studies were included. Of 5 included studies pertaining to tapentadol, 4 studies show tapentadol monotherapy to be effective for the treatment of diabetic peripheral neuropathy or chronic, radiating low back pain. Of the 3 studies included for buprenorphine, only one was a randomized controlled trial found not to have a statistically significant reduction in pain with TD buprenorphine likely due to very high withdrawal rates during the trial. Only 2 case reports were included from the available literature for levorphanol providing low-quality anecdotal evidence. The role of tapentadol, buprenorphine, and levorphanol for neuropathic pain conditions requires robust research including randomized controlled trials to evaluate their efficacy and safety.

The Regenerative Potential of Therapeutic Ultrasound on Neural Tissue: A Pragmatic Review.

OBJECTIVES: Low-intensity ultrasound (LIU)/low-intensity pulsed ultrasound (LIPUS) may influence nerve tissue regeneration and axonal changes in the context of carpal tunnel syndrome (CTS) and in the animal model. The purpose of this pragmatic review is to understand the current knowledge for the effects of low-intensity therapeutic ultrasound in the animal and human model and determine the future directions of this novel field. DESIGN: Pragmatic review. METHODS: We performed a literature search of available material using OVID, EmBase, and PubMed for LIU/LIPUS, all of which were preclinical trials, case reports, and case series using animal models. For CTS, a literature search was performed on PubMed (1954 to 2019), CENTRAL (the Cochrane Library, 1970 to 2018), Web of Science (1954 to 2019), and SCOPUS (1954 to 2019) to retrieve randomized controlled trials. RESULTS: Eight articles were discussed showing the potential effects of LIU on nerve regeneration in the animal model. Each of these trials demonstrated evidence of nerve regeneration in the animal model using LIPUS or LIU. Seven randomized controlled trials were reviewed for ultrasound effects for the treatment of carpal tunnel syndrome, each showing clinical efficacy comparable to other treatment modalities. CONCLUSIONS: LIU/LIPUS is a promising and noninvasive means of facilitating nerve regeneration in the animal model and in the treatment of carpal tunnel syndrome. Although many of the trials included in this review are preclinical, each demonstrates promising outcomes that could eventually be extrapolated into human studies.

The Effectiveness of Autologous Platelet-Rich Plasma for Osteoarthritis of the Hip: A Retrospective Analysis.

BACKGROUND: Platelet-rich plasma (PRP) is a minimally invasive treatment option to reduce pain and promote tissue healing. At the time this study was performed, there was limited published literature analyzing outcomes for patients treated with PRP for hip osteoarthritis. METHODS: Thirty-six patients aged 49-85 (66.0 ± 12.1) years with chronic hip pain who met inclusion criteria underwent image-guided intra-articular hip PRP injection. Outcomes were measured at baseline, two weeks, three months, and up to six months using the visual analog scale (VAS) for pain and the Hip Disability and Osteoarthritis Outcome Score (HOOS). The proportion of responders, as defined by a ≥50% reduction in VAS pain score, was assessed at three and six months. RESULTS: At two weeks, there was a significant improvement (P < 0.05) of function in two HOOS subscales: Symptoms and Activities of Daily Living. There was a significant improvement in all HOOS categories at six months. A significant improvement in VAS was observed at six months (baseline VAS = 6.9 ± 0.7 &→ 4.3 ± 1.8, 95% confidence interval = 2.0 to 3.2, P < 0.05). Sixty-seven percent (24/36) of the patients reported a ≥50% improvement in pain at three months; 58% (21/36) reported a ≥50% improvement in pain at six months. Stratification by Kellgren-Lawrence grades revealed that 86% and 82% of the KL grades 1 and 2 were responders at six months, respectively. CONCLUSIONS: In patients with mild/moderate hip osteoarthritis, PRP may provide pain relief and functional improvement for up to six months.

Regenerative Techniques for Neuraxial Back Pain: a Systematic Review.

PURPOSE OF REVIEW: Regenerative modalities have been identified in numerous clinical studies as beneficial in various settings. The focus of this review is to summarize key studies and current concepts for the role of regenerative medicine in the treatment of neuraxial back pain. RECENT FINDINGS: Recent studies have demonstrated the benefit of regenerative therapies for the treatment of neuraxial back pain. A literature review of clinical trials published between 2015 and 2017 was performed using OVID, PubMed, and Google Scholar to identify investigations attempting to determine the efficacy of various regenerative modalities on two primary sources of low back pain: facet arthropathy and degenerative disc disease. The seven articles analyzed in this systematic review present promising data regarding the use of these autologous biologic treatments, but many of these investigations have several limitations in common including small sample size. Regenerative medicine has been shown to demonstrate efficacy in the treatment of neuraxial back pain. As the field advances, new studies are needed comparing efficacy and safety profiles to better determine best practice techniques and standards in the future.

A patient navigation intervention for drug-involved former prison inmates.

BACKGROUND: Former prison inmates experience high rates of hospitalizations and death during the transition from prison to the community, particularly from drug-related causes and early after release. The authors designed a randomized controlled trial (RCT) of patient navigation to reduce barriers to health care and hospitalizations for former prison inmates. METHODS: Forty former prison inmates with a history of drug involvement were recruited and randomized within 15 days after prison release. Participants were randomized to receive 3 months of patient navigation (PN) with facilitated enrollment into an indigent care discount program (intervention) or facilitated enrollment into an indigent care discount program alone (control). Structured interviews were conducted at baseline, 3 months, and 6 months. Outcomes were measured as a change in self-reported barriers to care and as the rate of health service use per 100 person-days. RESULTS: The mean number of reported barriers to care was reduced at 3 and 6 months in both groups. At 6 months, the rate of emergency department/urgent care visits per 100 person-days since baseline was 1.1 among intervention participants and 0.5 among control participants (P = .04), whereas the rate of hospitalizations per 100 person-days was 0.2 in intervention participants and 0.6 in control participants (P = .04). CONCLUSIONS: Recruitment of former inmates into an RCT of patient navigation was highly feasible, but follow-up was limited by rearrests. Results suggest a significantly lower rate of hospitalizations among navigation participants, although the rate of emergency department/urgent care visits was not improved. Patient navigation is a promising, pragmatic intervention that may be effective at reducing high-cost health care utilization in former prison inmates.