Michael C. Rowbotham

Musculoskeletal pain and mobility disability are common in older adults, but relationships among pain parameters and physical performance are poorly understood. We quantified the impact of different pain measures—recalled and movement-evoked pain—on walk and stair climb time in older adults from the Study of Muscle, Mobility and Aging (SOMMA). In SOMMA (N = 879, age = 76.3 ± 5.0 years, 59% women, 84% non-Hispanic White), participants completed usual pace 400-m walk (avg = 6.6 ± 1.2 min) and stair climb tests (avg = 26.6 ± 7.2 s.). Assessments of recalled pain included the Brief Pain Inventory, total lower body pain, and Neuropathy Total Symptom Score. Movement-evoked pain was assessed separately for the 400-m walk and stair climb tasks. Multivariable linear regression modeled the associations of pain with time to complete the tasks, reported as β [95%CI] expressed per SD increment of pain measure or per pain categories, adjusted for age, sex, race/ethnicity, BMI, prescription medications, and depressive symptoms. A greater degree of any pain measure was associated with longer (worse) physical performance time. For each SD increment in lower body pain (back, hips, knees, feet/ankles), participants had longer walk (+ 10.5 s [6.1, 14.8]) and stair climb time (+ 0.6 s [0.1, 1.1]). Compared to participants with no pain, walk time was longer in those with resting pain (+ 22.8 s [4.9,40.6]) and movement-evoked pain (+ 19.1 s [8.9, 29.2]) but not movement-evoked hypoalgesia (+ 12.6 s [−4.4, 29.7]); stair climb showed similar patterns. Different pain assessments captured heterogeneous pain contextual factors (e.g., type, state, temporality) among these older adults. However, all pain measures were similarly associated with physical performance, suggesting that multiple assessments may provide a more comprehensive characterization of pain and physical function outcomes.

We describe our institutional experience of developing a liquid biopsy approach using circulating tumor DNA (ctDNA) analysis for personalized medicine in cancer patients, focusing on the hurdles encountered during the multistep process in order to benefit other investigators wishing to set up this type of study in their institution. Blood samples were collected at the time of cancer surgery from 209 patients with one of nine different cancer types. Extracted tumor DNA and circulating cell-free DNA were sequenced using cancer-specific panels and the Illumina MiSeq machine. Almost half of the pairs investigated were uninformative, mostly because there was no trackable pathogenic mutation detected in the original tumor. The pairs with interpretable data corresponded to 107 patients. Analysis of 48 gene sequences common to both panels was performed and revealed that about 40% of these pairs contained at least one driver mutation detected in the DNA extracted from plasma. Here, we describe the choice of our overall approach, the selection of the cancer panels, and the difficulties encountered during the multistep process, including the use of several tumor types and in the data analysis. We also describe some case reports using longitudinal samples, illustrating the potential advantages and rewards in performing ctDNA sequencing to monitor tumor burden or guide treatment for cancer patients.

Background: The effect of pregabalin on acute herpes zoster pain has not been previously evaluated. Methods: In a randomized, double-blind, placebo-controlled, two-session crossover study the effect of a single oral dose of pregabalin (150 mg) on pain and allodynia was evaluated in 8 subjects with herpes zoster. Results: Over 6 hours of observation, pain decreased by a mean of 33% with pregabalin and 14% with placebo (p < 0.10). Effects on allodynia and SF-MPQ were not significant. Conclusions: Compared to an earlier study of gabapentin 900 mg for acute zoster pain and allodynia that followed a nearly identical protocol, pregabalin had a similar effect on pain and was well tolerated, with no difference from placebo on sleepiness. Common side effects of light-headedness, unsteady gait, and slowed thinking were almost identical to that observed in the earlier study of gabapentin. Subject recruitment proved difficult in part due to the widespread off-label use of gabapentin and pregabalin for acute zoster pain in our region of the USA. Trial Registration: ClinicalTrials.gov Identifier: NCT00352651

ABT-594 is a neuronal nicotinic acetylcholine receptor (NNR) agonist that exhibits potent analgesic activity in preclinical models of acute, chronic, and neuropathic pain. The purpose of this phase 2, randomized, multicenter, double-blind, placebo-controlled study was to evaluate the safety and analgesic efficacy of ABT-594 in patients with diabetic peripheral neuropathic pain (DPNP). A total of 266 DPNP patients were randomized 1:1:1:1 to receive placebo, ABT-594 150 microg BID, ABT-594 225 microg BID, or ABT-594 300 microg BID. Patients were titrated to a fixed-dose of ABT-594 over 7 days and remained at this dose for another 6 weeks. Compared to placebo, all three ABT-594 treatment groups showed significantly greater decreases on the average diary-based 0-10 Pain Rating Scale (PRS) score from baseline to final evaluation, the primary efficacy measure (placebo, -1.1; 150 microg BID, -1.9; 225 microg BID, -1.9; 300 microg BID, -2.0). The proportion of patients achieving at least a 50% improvement in the average diary-based PRS was greater in all three ABT-594 treatment groups. However, adverse event (AE) dropout rates were significantly higher in all three ABT-594 treatment groups (28% for 150 microg BID, 46% for 225 microg BID, and 66% for 300 microg BID) than for the placebo group (9%). Consistent with the expected side-effect profile of NNR agonists, the most frequently reported AEs were nausea, dizziness, vomiting, abnormal dreams, and asthenia. This study establishes proof of concept for NNR agonists as a new class of compounds for treating neuropathic pain.