Distraction analgesia in chronic pain patients: the impact of catastrophizing.

BACKGROUND: Diverting attention away from noxious stimulation (i.e., distraction) is a common pain-coping strategy. Its effects are variable across individuals, however, and the authors hypothesized that chronic pain patients who reported higher levels of pain catastrophizing would derive less pain-reducing benefit from distraction. METHODS: Chronic pain patients (n=149) underwent psychometric and quantitative sensory testing, including assessment of the temporal summation of pain in the presence and absence of a distracting motor task. RESULTS: A simple distraction task decreased temporal summation of pain overall, but, surprisingly, a greater distraction analgesia was observed in high catastrophizers. This enhanced distraction analgesia in high catastrophizers was not altered when controlling for current pain scores, depression, anxiety, or opioid use (analysis of covariance [ANCOVA]: F=8.7, P<0.005). Interestingly, the magnitude of distraction analgesia was inversely correlated with conditioned pain modulation (Pearson R=-0.23, P=0.005). CONCLUSION: Distraction produced greater analgesia among chronic pain patients with higher catastrophizing, suggesting that catastrophizing's pain-amplifying effects may be due in part to greater attention to pain, and these patients may benefit from distraction-based pain management approaches. Furthermore, these data suggest that distraction analgesia and conditioned pain modulation may involve separate underlying mechanisms.

Lysosomal-mediated waste clearance in retinal pigment epithelial cells is regulated by CRYBA1/ßA3/A1-crystallin via V-ATPase-MTORC1 signaling.

In phagocytic cells, including the retinal pigment epithelium (RPE), acidic compartments of the endolysosomal system are regulators of both phagocytosis and autophagy, thereby helping to maintain cellular homeostasis. The acidification of the endolysosomal system is modulated by a proton pump, the V-ATPase, but the mechanisms that direct the activity of the V-ATPase remain elusive. We found that in RPE cells, CRYBA1/ßA3/A1-crystallin, a lens protein also expressed in RPE, is localized to lysosomes, where it regulates endolysosomal acidification by modulating the V-ATPase, thereby controlling both phagocytosis and autophagy. We demonstrated that CRYBA1 coimmunoprecipitates with the ATP6V0A1/V0-ATPase a1 subunit. Interestingly, in mice when Cryba1 (the gene encoding both the ßA3- and ßA1-crystallin forms) is knocked out specifically in RPE, V-ATPase activity is decreased and lysosomal pH is elevated, while cathepsin D (CTSD) activity is decreased. Fundus photographs of these Cryba1 conditional knockout (cKO) mice showed scattered lesions by 4 months of age that increased in older mice, with accumulation of lipid-droplets as determined by immunohistochemistry. Transmission electron microscopy (TEM) of cryba1 cKO mice revealed vacuole-like structures with partially degraded cellular organelles, undigested photoreceptor outer segments and accumulation of autophagosomes. Further, following autophagy induction both in vivo and in vitro, phospho-AKT and phospho-RPTOR/Raptor decrease, while pMTOR increases in RPE cells, inhibiting autophagy and AKT-MTORC1 signaling. Impaired lysosomal clearance in the RPE of the cryba1 cKO mice also resulted in abnormalities in retinal function that increased with age, as demonstrated by electroretinography. Our findings suggest that loss of CRYBA1 causes lysosomal dysregulation leading to the impairment of both autophagy and phagocytosis.

Alteration in pain modulation in women with persistent pain after lumpectomy: influence of catastrophizing.

CONTEXT: Persistent pain is common after surgical treatment of breast cancer, but fairly little is known about the changes in sensory processing that accompany such pain syndromes. OBJECTIVES: This study used quantitative sensory testing to compare psychophysical responses to standardized noxious stimulation in two groups of women who had previously undergone breast cancer surgery: women with (n=37) and without (n=34) persistent postoperative pain. METHODS: Participants underwent a single testing session in which responses to a variety of noxious stimuli were assessed. RESULTS: Findings suggested that women with chronic pain after breast cancer surgery display enhanced temporal summation of mechanical pain, deficits in endogenous pain inhibition, and more intense painful aftersensations compared with those without long-term pain. Some of these group differences were mediated by higher levels of pain catastrophizing in the group of women with persistent pain. CONCLUSION: These findings suggest that persistent postoperative pain is associated with alterations in central nervous system pain-modulatory processes. Future treatment studies might benefit from targeting these pain-modulatory systems, and additional studies using functional neuroimaging methods might provide further valuable information about the pathophysiology of long-term postsurgical pain in women treated for breast cancer.

Evoked pain analgesia in chronic pelvic pain patients using respiratory-gated auricular vagal afferent nerve stimulation.

OBJECTIVE: Previous vagus nerve stimulation (VNS) studies have demonstrated antinociceptive effects, and recent noninvasive approaches, termed transcutaneous-vagus nerve stimulation (t-VNS), have utilized stimulation of the auricular branch of the vagus nerve in the ear. The dorsal medullary vagal system operates in tune with respiration, and we propose that supplying vagal afferent stimulation gated to the exhalation phase of respiration can optimize t-VNS. DESIGN: Counterbalanced, crossover study. PATIENTS: Patients with chronic pelvic pain (CPP) due to endometriosis in a specialty pain clinic. INTERVENTIONS/OUTCOMES: We evaluated evoked pain analgesia for respiratory-gated auricular vagal afferent nerve stimulation (RAVANS) compared with nonvagal auricular stimulation (NVAS). RAVANS and NVAS were evaluated in separate sessions spaced at least 1 week apart. Outcome measures included deep-tissue pain intensity, temporal summation of pain, and anxiety ratings, which were assessed at baseline, during active stimulation, immediately following stimulation, and 15 minutes after stimulus cessation. RESULTS: RAVANS demonstrated a trend for reduced evoked pain intensity and temporal summation of mechanical pain, and significantly reduced anxiety in N = 15 CPP patients, compared with NVAS, with moderate to large effect sizes (η(2) > 0.2). CONCLUSION: Chronic pain disorders such as CPP are in great need of effective, nonpharmacological options for treatment. RAVANS produced promising antinociceptive effects for quantitative sensory testing (QST) outcomes reflective of the noted hyperalgesia and central sensitization in this patient population. Future studies should evaluate longer-term application of RAVANS to examine its effects on both QST outcomes and clinical pain.

Elevated pain sensitivity in chronic pain patients at risk for opioid misuse.

UNLABELLED: This study employed quantitative sensory testing (QST) to evaluate pain responses in chronic spinal pain patients at low risk and high risk for opioid misuse, with risk classification based on scores on the Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R). Patients were further subgrouped according to current use of prescription opioids. Of the 276 chronic pain patients tested, approximately 65% were taking opioids; a median split was used to further categorize these patients as being on lower or higher doses of opioids. The high-risk group (n = 161) reported higher levels of clinical pain, had lower pressure and thermal pain thresholds at multiple body sites, had lower heat pain tolerance, and rated repetitive mechanical stimuli as more painful relative to the low-risk group (n = 115; P's < .01). In contrast, QST measures did not differ across opioid groups. Multiple linear regression analysis suggested that indices of pain-related distress (ie, anxiety and catastrophizing about pain) were also predictive of hyperalgesia, particularly in patients taking opioids. Collectively, regardless of opioid status, the high-risk group was hyperalgesic relative to the low-risk group; future opioid treatment studies may benefit from the classification of opioid risk, and the examination of pain sensitivity and other factors that differentiate high- and low-risk groups. PERSPECTIVE: This study demonstrates that chronic spinal pain patients at high risk for misuse of prescription opioids are more pain-sensitive than low-risk patients, whether or not they are currently taking opioids. Indices of pain-related distress were important predictors of pain sensitivity, particularly among those patients taking opioids for pain.

Alterations in pain responses in treated and untreated patients with restless legs syndrome: associations with sleep disruption.

OBJECTIVE: There has been recent interest in characterizing potential abnormalities of pain processing in patients with sleep disorders such as Restless Legs Syndrome (RLS). The aim of this study was to evaluate psychophysical responses to noxious heat and pressure stimuli in both treated and untreated RLS patients, compared to matched controls. METHODS: This study is a cross-sectional group comparison of RLS patients with matched controls. A total of 31 patients (15 treated, 16 untreated) with a confirmed diagnosis of RLS were compared to 18 controls with no history of RLS or related sleep disorders. RESULTS: RLS patients (both treated and untreated) demonstrated reduced pain thresholds and reported greater clinical pain relative to controls. Moreover, RLS patients demonstrated enhanced temporal summation of heat pain (p<.05), which may reflect aberrant central nervous system facilitation of pain transmission. Both treated and untreated RLS patients reported disrupted sleep relative to controls, and mediation analyses suggested that the reduced pain thresholds in RLS were attributable to sleep disturbance. However, the effect of RLS on the magnitude of temporal summation of heat pain was independent of sleep disturbance. CONCLUSIONS: These findings suggest that central nervous system pain processing may be amplified in RLS, perhaps partially as a consequence of sleep disruption. RLS patients, even those whose symptoms are managed pharmacologically, may be at elevated long-term risk for the development or maintenance of persistent pain conditions. Further studies in larger samples could help to improve the prospects for pain management in RLS patients.