The neuroinflammatory component of negative affect in patients with chronic pain.

Negative affect (NA) is a significant cause of disability for chronic pain patients. While little is known about the mechanism underlying pain-comorbid NA, previous studies have implicated neuroinflammation in the pathophysiology of both depression and chronic pain. Here, we tested the hypothesis that NA in pain patients is linked to elevations in the brain levels of the glial marker 18 kDa translocator protein (TSPO), and changes in functional connectivity. 25 cLBP patients (42.4 ± 13 years old; 13F, 12M) with chronic low back pain (cLBP) and 27 healthy control subjects (48.9 ± 13 years old; 14F, 13M) received an integrated (i.e., simultaneous) positron emission tomography (PET)/magnetic resonance imaging (MRI) brain scan with the second-generation TSPO ligand [11C]PBR28. The relationship between [11C]PBR28 signal and NA was assessed first with regression analyses against Beck Depression Inventory (BDI) scores in patients, and then by comparing cLBP patients with little-to-no, or mild-to-moderate depression against healthy controls. Further, the relationship between PET signal, BDI and frontolimbic functional connectivity was evaluated in patients with mediation models. PET signal was positively associated with BDI scores in patients, and significantly elevated in patients with mild-to-moderate (but not low) depression compared with controls, in anterior middle and pregenual anterior cingulate cortices (aMCC, pgACC). In the pgACC, PET signal was also associated with this region's functional connectivity to the dorsolateral PFC (pgACC-dlPFC), and mediated of the association between pgACC-dlPFC connectivity and BDI. These observations support a role for glial activation in pain-comorbid NA, identifying in neuroinflammation a potential therapeutic target for this condition.

Changes in Pain Sensitivity and Pain Modulation During Oral Opioid Treatment: The Impact of Negative Affect.

OBJECTIVE: Opioids are frequently prescribed for chronic low back pain (CLBP), but there are broad individual differences in the benefits and risks of opioid therapy, including the development opioid-induced hyperalgesia. This study examined quantitative sensory testing (QST) data among a group of CLBP patients undergoing sustained oral opioid treatment. We investigated whether individual differences in psychological characteristics were related to opioid-induced changes in pain perception and pain modulation. DESIGN: The six-month, open-label trial evaluated patients with low to high levels of negative affect (e.g., symptoms of distress, depression and anxiety); participants underwent QST at baseline (prior to initiating treatment) and during oral opioid treatment. SETTING: A chronic pain management center. PATIENTS: The 31 study participants had chronic discogenic back pain, with a pain intensity rating >3/10. Participants were divided into groups with high vs. low levels of Negative Affect (NA). RESULTS: In the previously-published manuscript describing the clinical outcomes of the trial, high NA patients achieved only about half of the analgesic effect observed in the low NA group (Wasan AD, Michna E, Edwards RR, et al. Psychiatric comorbidity is associated prospectively with diminished opioid analgesia and increased opioid misuse in patients with chronic low back pain. Anesthesiology 2015;123:861-72). The QST findings reported here suggested that tolerance to experimental (cold pressor) pain and conditioned pain modulation tended to decrease in the high NA group over the course of opioid treatment, while temporal summation of mechanical pain declined in the low NA group. CONCLUSIONS: These results reveal that while the low NA group seemed to exhibit a generally adaptive, analgesic pattern of changes during opioid management, the high NA group showed a pattern more consistent with opioid-induced hyperalgesic processes. A greater susceptibility to hyperalgesia-promoting changes in pain modulation among patients with high levels of distress may contribute to a lower degree of benefit from opioid treatment in high NA patients.

Catastrophic thinking and increased risk for prescription opioid misuse in patients with chronic pain.

BACKGROUND: As a consequence of the substantial rise in the prescription of opioids for the treatment of chronic noncancer pain, greater attention has been paid to the factors that may be associated with an increased risk for prescription opioid misuse. Recently, a growing number of studies have shown that patients with high levels of catastrophizing are at increased risk for prescription opioid misuse. OBJECTIVE: The primary objective of this study was to examine the variables that might underlie the association between catastrophizing and risk for prescription opioid misuse in patients with chronic pain. METHODS: Patients with chronic musculoskeletal pain (n=115) were asked to complete the SOAPP-R, a validated self-report questionnaire designed to identify patients at risk for prescription opioid misuse. Patients were also asked to complete self-report measures of pain intensity, catastrophizing, anxiety, and depression. RESULTS: Consistent with previous research, we found that catastrophizing was associated with an increased risk for prescription opioid misuse. Results also revealed that the association between catastrophizing and risk for opioid misuse was partially mediated by patients' levels of anxiety. Follow-up analyses, however, indicated that catastrophizing remained a significant 'unique' predictor of risk for opioid misuse even when controlling for patients' levels of pain severity, anxiety and depressive symptoms. DISCUSSION: Discussion addresses the factors that might place patients with high levels of catastrophizing at increased risk for prescription opioid misuse. The implications of our findings for the management of patients considered for opioid therapy are also discussed.

Femoral nailing with transverse locking screws through the femoral neck.

We treated 55 patients with subtrochanteric or comminuted femoral fractures with a transverse locking femoral nail (Alta, Howmedica). This nail was positioned more cephalad than usual so that at least one fixation screw was located in the femoral neck or head. Forty-seven fractures (20 subtrochanteric and 27 diaphyseal) were available for follow-up averaging 12 months (3-35). The time to radiographic healing averaged 7 months (3-21). There was one delayed union, one non-union, two superficial infections, one broken proximal screw, one compartment syndrome of the thigh, and one peroneal nerve palsy. There were no femoral neck fractures, avascular changes of the femoral head, or gluteal irritation at the most recent follow up. The described technique appears safe and effective, is technically easy, and avoids intra-articular screws.