Theoretical Grounds of Pain Tracker Self Manager: An Acceptance and Commitment Therapy Digital Intervention for Patients with Chronic Pain.

OBJECTIVE: To report the theoretical basis and design of a novel digital Acceptance and Commitment Therapy (ACT) intervention for people with chronic pain, the Pain Tracker Self Manager (PTSM), which had promising efficacy in a recent pilot trial. METHODS: Content development by a multidisciplinary panel of experts in psychiatry, clinical psychology, nursing and social work, with feedback from a group of patients with chronic pain and their providers. Materials included paper-based sketching of a story character, visual metaphors, and a series of stories designed to deliver the theory-based components of our behavioral intervention. RESULTS: This development and design process resulted in 4 digitally delivered clinical modules that combine visual and verbal cues. In addition, it generated a series of novel ACT metaphors specifically tailored to patients with chronic pain: Pain: Injury vs. Threat, Life Navigation System, The Fog of Pain, and Get Rhythm. Consistent with ACT theory and the contextual behavioral science framework, PTSM utilized: perspective-taking, values clarification, acceptance strategies, and nursing and psychological care recommendations. DISCUSSION: Reports of the design and theoretical basis of digital health interventions are highly needed to increase the rigor of their development process and more progressively advance our body of knowledge. This pilot study developed and tested a series of ACT metaphors that can be readily used by ACT clinicians working with this population. CONCLUSION: PTSM is a novel digital ACT intervention for patients with chronic pain with features directly linked to ACT processes and theory.

Quantitative Proteomics of Clinically Relevant Drug-Metabolizing Enzymes and Drug Transporters and Their Intercorrelations in the Human Small Intestine.

The levels of drug-metabolizing enzymes (DMEs) and transporter proteins in the human intestine are pertinent to determine oral drug bioavailability. Despite the paucity of reports on such measurements, it is well recognized that these values are essential for translating in vitro data on drug metabolism and transport to predict drug disposition in gut wall. In the current study, clinically relevant DMEs [cytochrome P450 (P450) and uridine 5'-diphospho-glucuronosyltransferase (UGT)] and drug transporters were quantified in total mucosal protein preparations from the human jejunum (n = 4) and ileum (n = 12) using quantification concatemer-based targeted proteomics. In contrast to previous reports, UGT2B15 and organic anion-transporting polypeptide 1 (OATP1A2) were quantifiable in all our samples. Overall, no significant disparities in protein expression were observed between jejunum and ileum. Relative mRNA expression for drug transporters did not correlate with the abundance of their cognate protein, except for P-glycoprotein 1 (P-gp) and organic solute transporter subunit alpha (OST-α), highlighting the limitations of RNA as a surrogate for protein expression in dynamic tissues with high turnover. Intercorrelations were found within P450 [2C9-2C19 (P = 0.002, R 2 = 0.63), 2C9-2J2 (P = 0.004, R 2 = 0.40), 2D6-2J2 (P = 0.002, R 2 = 0.50)] and UGT [1A1-2B7 (P = 0.02, R 2 = 0.87)] family of enzymes. There were also correlations between P-gp and several other proteins [OST-α (P < 0.0001, R 2 = 0.77), UGT1A6 (P = 0.009, R 2 = 0.38), and CYP3A4 (P = 0.007, R 2 = 0.30)]. Incorporating such correlations into building virtual populations is crucial for obtaining plausible characteristics of simulated individuals. SIGNIFICANCE STATEMENT: A number of drug transporters were quantified for the first time in this study. Several intercorrelations of protein abundance were reported. mRNA expression levels proved to be a poor reflection of differences between individuals regarding the level of protein expression in gut. The reported abundance of drug-metabolizing enzymes and transporters and their intercorrelations will contribute to better predictions of oral drug bioavailability and drug-drug interactions by linking in vitro observations to potential outcomes through physiologically based pharmacokinetic models.

A Controlled Pilot Trial of PainTracker Self-Manager, a Web-Based Platform Combined With Patient Coaching, to Support Patients' Self-Management of Chronic Pain.

The objective of this study was to develop and pilot test a chronic pain empowerment and self-management platform, derived from acceptance and commitment therapy, in a pain specialty setting. A controlled, sequential, nonrandomized study design was used to accommodate intervention development and to test the efficacy of the PainTracker Self-Manager (PTSM) intervention (Web-based educational modules and outcome tracking combined with tailored patient coaching sessions and provider guidance). Generalized estimating equations evaluated changes over time (baseline, 3 months, 6 months) in pain self-efficacy (primary outcome), chronic pain acceptance (activity engagement and pain willingness), perceived efficacy in patient-provider interactions, pain intensity and interference, and overall satisfaction with pain treatment (secondary outcomes) between intervention (n = 48) and usual care control groups (n = 51). The full study sample (N = 99) showed greater improvements over time (significant Group × Time interactions) in pain self-efficacy and satisfaction with pain treatment. Among study completers (n = 82), greater improvement in activity engagement as well as pain intensity and interference were also observed. These preliminary findings support the efficacy of the PTSM intervention in a pain specialty setting. Further research is needed to refine and expand the PTSM intervention and to test it in a randomized trial in primary care settings. PERSPECTIVE: We developed a Web-based patient empowerment platform that combined acceptance and commitment therapy-based educational modules and tailored coaching sessions with longitudinal tracking of treatments and patient-reported outcomes, named PTSM. Pilot controlled trial results provide preliminary support for its efficacy in improving pain self-efficacy, activity engagement, pain intensity and interference, and satisfaction with pain treatment.

Opioids for pain management in older adults: Strategies for safe prescribing.

Appropriate selection and dosing of medications is essential when prescribing for older adults. Opioids are commonly employed to treat pain but must be approached with caution due to potentially dangerous adverse reactions. This article provides strategies for safely prescribing opioids for pain in older adults.

Pharmacologic pain management at the end of life.

Escalating pain is common in the final weeks of life, requiring skilled management to assist patients with a life-limiting illness. Using a cancer model, pharmacologic approaches to treat pain in the final weeks of life are reviewed.

Pain in cancer survivors.

Pain is a common problem in cancer survivors, especially in the first few years after treatment. In the longer term, approximately 5% to 10% of survivors have chronic severe pain that interferes with functioning. The prevalence is much higher in certain subpopulations, such as breast cancer survivors. All cancer treatment modalities have the potential to cause pain. Currently, the approach to managing pain in cancer survivors is similar to that for chronic cancer-related pain, pharmacotherapy being the principal treatment modality. Although it may be appropriate to continue strong opioids in survivors with moderate to severe pain, most pain problems in cancer survivors will not require them. Moreover, because more than 40% of cancer survivors now live longer than 10 years, there is growing concern about the long-term adverse effects of opioids and the risks of misuse, abuse, and overdose in the nonpatient population. As with chronic nonmalignant pain, multimodal interventions that incorporate nonpharmacologic therapies should be part of the treatment strategy for pain in cancer survivors, prescribed with the aim of restoring functionality, not just providing comfort. For patients with complex pain issues, multidisciplinary programs should be used, if available. New or worsening pain in a cancer survivor must be evaluated to determine whether the cause is recurrent disease or a second malignancy. This article focuses on patients with a history of cancer who are beyond the acute diagnosis and treatment phase and on common treatment-related pain etiologies. The benefits and harms of the various pharmacologic and nonpharmacologic options for pain management in this setting are reviewed.

Chronic pain management in the cancer survivor: tips for primary care providers.

Many cancer survivors suffer from chronic pain related to treatment. Pain management in the survivor is similar to chronic noncancer pain, with the important caveat that new or worsening pain must be promptly assessed for malignancy. This article reviews cancer survivorship, identifies common pain problems, and discusses strategies for management.

Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain.

UNLABELLED: Use of chronic opioid therapy for chronic noncancer pain has increased substantially. The American Pain Society and the American Academy of Pain Medicine commissioned a systematic review of the evidence on chronic opioid therapy for chronic noncancer pain and convened a multidisciplinary expert panel to review the evidence and formulate recommendations. Although evidence is limited, the expert panel concluded that chronic opioid therapy can be an effective therapy for carefully selected and monitored patients with chronic noncancer pain. However, opioids are also associated with potentially serious harms, including opioid-related adverse effects and outcomes related to the abuse potential of opioids. The recommendations presented in this document provide guidance on patient selection and risk stratification; informed consent and opioid management plans; initiation and titration of chronic opioid therapy; use of methadone; monitoring of patients on chronic opioid therapy; dose escalations, high-dose opioid therapy, opioid rotation, and indications for discontinuation of therapy; prevention and management of opioid-related adverse effects; driving and work safety; identifying a medical home and when to obtain consultation; management of breakthrough pain; chronic opioid therapy in pregnancy; and opioid-related policies. PERSPECTIVE: Safe and effective chronic opioid therapy for chronic noncancer pain requires clinical skills and knowledge in both the principles of opioid prescribing and on the assessment and management of risks associated with opioid abuse, addiction, and diversion. Although evidence is limited in many areas related to use of opioids for chronic noncancer pain, this guideline provides recommendations developed by a multidisciplinary expert panel after a systematic review of the evidence.

Treatment response in antidepressant-naïve postherpetic neuralgia patients: double-blind, randomized trial.

UNLABELLED: In 47 patients with postherpetic neuralgia (PHN) who had never had an adequate trial of any antidepressant, we performed a randomized, double-blind, parallel design trial comparing desipramine, amitriptyline, and fluoxetine. Patients were titrated to a maximum of 150 mg/day for desipramine and amitriptyline and 60 mg/day for fluoxetine over a 3-week period and then treated for an additional 3 weeks before tapering off study medication. A total of 38 subjects (81%) completed the entire trial. The modified intent-to-treat analysis of percent change in daily diary pain intensity scores showed no significant differences among the 3 drugs (ANOVA P = .120). Desipramine produced the greatest reduction in pain intensity (47%), followed by amitriptyline (38%) and fluoxetine (35%). Clinically meaningful pain relief (moderate or better) was significantly more likely with desipramine (12/15 patients) than with amitriptyline (9/17) or fluoxetine (5/15); chi(2)P = 0.036). The 11 subjects using opioids at study entry had smaller reductions in pain than those not using concomitant opioids. The fluoxetine group had the highest noncompletion rate (33%), with 1 subject hospitalized for hyponatremia. Although the magnitude of pain reduction and the category pain relief rating was not significantly different among the 3 drugs, the tricyclics desipramine and amitriptyline were well tolerated and provided clinically meaningful pain relief in 53% to 80% of subjects. PERSPECTIVE: Few clinical trials focus on patients who are naïve to an entire class of medication. In this randomized blinded trial, the tricyclic antidepressants desipramine and amitriptyline were compared to the serotonin-selective antidepressant fluoxetine. All 3 drugs reduced PHN pain, with desipramine providing satisfactory relief in 80% of those treated.

Review of lidocaine patch 5% studies in the treatment of postherpetic neuralgia.

Postherpetic neuralgia (PHN) is a chronic pain syndrome that disproportionately affects the elderly; its incidence is anticipated to increase as the population ages. PHN presents as pain (continuous burning or intense paroxysmal), most often with tactile allodynia, which may be severe and disabling, resulting in poor quality of life and depression. Traditional treatments have included tricyclic antidepressants, anticonvulsants and opioids; however, adverse systemic effects associated with these agents have led to the development of a newer and potentially safer agent, the topical lidocaine patch 5% (Lidoderm), a targeted peripheral analgesic. This article reviews the clinical pharmacology of the lidocaine patch 5% for the treatment of PHN and summarises data from clinical trials of its safety, tolerability and efficacy. The Medline search terms "lidocaine" and "patch" were used to search for English-language articles on the pharmacokinetics of the lidocaine patch 5% and its clinical use for the treatment of PHN. Additional published studies not identified by the database search but performed by the authors or their colleagues were also included in the review. The systemic absorption of lidocaine from the patch was minimal in healthy adults when four patches were applied for up to 24 hours/day, and lidocaine absorption was even lower among PHN patients than healthy adults at the currently recommended dose. Vehicle-controlled and open-label trials found the lidocaine patch 5%, either alone or in combination with other agents, to be effective in the treatment of PHN. Most adverse events were at patch application sites; no clinically significant systemic adverse effects were noted, including when used long term or in an elderly population.In patients with PHN, the lidocaine patch 5% has demonstrated relief of pain and tactile allodynia with a minimal risk of systemic adverse effects or drug-drug interactions. Because of its proven efficacy and safety profile, the lidocaine patch 5% has been recommended as a first-line therapy for the treatment of the neuropathic pain of PHN.

Oral opioid therapy for chronic peripheral and central neuropathic pain.

BACKGROUND: Although opioids are commonly used to treat chronic neuropathic pain, there are limited data to guide their use. Few controlled trials have been performed, and many types of neuropathic pain remain unstudied. METHODS: Adults with neuropathic pain that was refractory to treatment were randomly assigned to receive either high-strength (0.75-mg) or low-strength (0.15-mg) capsules of the potent mu-opioid agonist levorphanol for eight weeks under double-blind conditions. Intake was titrated by the patient to a maximum of 21 capsules of either strength per day. Outcome measures included the intensity of pain as recorded in a diary, the degree of pain relief, quality of life, psychological and cognitive function, the number of capsules taken daily, and blood levorphanol levels. RESULTS: Among the 81 patients exposed to the study drug, high-strength levorphanol capsules reduced pain by 36 percent, as compared with a 21 percent reduction in pain in the low-strength group (P=0.02). On average, patients in the high-strength group took 11.9 capsules per day (8.9 mg per day) and patients in the low-strength group took close to the 21 allowed (18.3 capsules per day; 2.7 mg per day). Affective distress and interference with functioning were reduced, and sleep was improved, but there were no differences between the high-strength group and the low-strength group in terms of these variables. Noncompletion of the study was primarily due to side effects of the opioid. Patients with central pain after stroke were the least likely to report benefit. CONCLUSIONS: The reduction in the intensity of neuropathic pain was significantly greater during treatment with higher doses of opioids than with lower doses. Higher doses produced more side effects without significant additional benefit in terms of other outcome measures.

The lidocaine patch 5% effectively treats all neuropathic pain qualities: results of a randomized, double-blind, vehicle-controlled, 3-week efficacy study with use of the neuropathic pain scale.

BACKGROUND: Several controlled clinical trials have demonstrated the efficacy and safety of the lidocaine patch 5% (LP) for the treatment of postherpetic neuralgia (PHN). OBJECTIVE: To assess the effects of the LP on distinct neuropathic pain qualities common to all neuropathic pain conditions, the authors analyzed data from one of the vehicle-controlled trials in which the Neuropathic Pain Scale (NPS), the only assessment tool specifically designed to measure the distinct components of neuropathic pain, was administered. METHODS AND RESULTS: To improve the sensitivity of the NPS to treatment effects, only patients who, at the time of enrollment in the study, reported moderate-to-severe pain on the NPS (as defined by a score > or =4/10 reported for at least 6 of the 10 individual NPS items) were included in the analysis. Thus, 96 patients were included in this analysis. After a 3-week, vehicle-controlled study, LP improved all assessed pain qualities to a greater extent than the placebo patch, as measured by the NPS 10, a sum score including all 10 NPS item scores ( = 0.043), and an NPS 8 score, which included scores for all 8 pain descriptors, excluding "unpleasantness" and "global intensity" ( = 0.042). Separate analysis of all 8 items believed not to reflect allodynia (NPS NA; excluding "skin sensitivity" and "surface pain") also demonstrated superiority ( = 0.022), as did analysis of the subitems that are believed not to be primarily related to peripheral pathophysiological events (the "NPS 4": "sharp," "hot," "dull," and "deep" pains; = 0.013). CONCLUSIONS: This study demonstrates that LP reduces the intensity of all common neuropathic pain qualities and thus may be of potential benefit for nonallodynic neuropathic pain states. Furthermore, these findings suggest that peripheral mechanisms may play a role in the pathophysiological development of pain qualities that heretofore have been assumed not to involve peripheral mechanisms, such as "dull," "deep," "sharp," and "burning" pains.

Systemic absorption of topical lidocaine in normal volunteers, patients with post-herpetic neuralgia, and patients with acute herpes zoster.

Topical lidocaine has been recently marketed as a new treatment for post-herpetic neuralgia. The aim of our study was to characterize the absorption profile of and systemic exposure to lidocaine from patch and gel formulations in normal volunteers, patients with post-herpetic neuralgia, and patients with acute herpes zoster. The bioavailability of lidocaine from the patch formulation averaged 3%, and was similar after single and repeated doses. Systemic exposure to lidocaine and monoethylglycinexylidide (MEGX), the primary active metabolite of lidocaine, after application of lidocaine gel or patches was minimal in normal volunteers, patients with post-herpetic neuralgia, and patients with acute herpes zoster. Considering the benefit versus risk of topical lidocaine, systemic absorption and toxicity of lidocaine seems not to be a significant risk.

Lidocaine patch: double-blind controlled study of a new treatment method for post-herpetic neuralgia.

Post-herpetic neuralgia (PHN) is a common and often intractable neuropathic pain syndrome predominantly affecting the elderly. Topical local anesthetics have shown promise in both uncontrolled and controlled studies. Thirty-five subjects with established PHN affecting the torso or extremities completed a four-session, random order, double-blind, vehicle-controlled study of the analgesic effects of topically applied 5% lidocaine in the form of a non-woven polyethylene adhesive patch. All subjects had allodynia on examination. Up to 3 patches, covering a maximum of 420 cm2, were applied to cover the area of greatest pain as fully as possible. Lidocaine containing patches were applied in two of the four 12-h-long sessions, in one session vehicle patches were applied, and one session was a no-treatment observation session. Lidocaine containing patches significantly reduced pain intensity at all time points 30 min to 12 h compared to no-treatment observation, and at all time points 4--12 h compared to vehicle patches. Lidocaine patches were superior to both no-treatment observation and vehicle patches in averaged category pain relief scores. The highest blood lidocaine level measured was 0.1 micrograms/ml, indicating minimal systemic absorption of lidocaine. Patch application was without systemic side effect and well tolerated when applied on allodynic skin for 12 h. This study demonstrates that topical 5% lidocaine in patch form is easy to use and relieves post-herpetic neuralgia.