Biological and behavioral markers of pain following nerve injury in humans.

The evolution of peripheral and central changes following a peripheral nerve injury imply the onset of afferent signals that affect the brain. Changes to inflammatory processes may contribute to peripheral and central alterations such as altered psychological state and are not well characterized in humans. We focused on four elements that change peripheral and central nervous systems following ankle injury in 24 adolescent patients and 12 age-sex matched controls. Findings include (a) Changes in tibial, fibular, and sciatic nerve divisions consistent with neurodegeneration; (b) Changes within the primary motor and somatosensory areas as well as higher order brain regions implicated in pain processing; (c) Increased expression of fear of pain and pain reporting; and (d) Significant changes in cytokine profiles relating to neuroinflammatory signaling pathways. Findings address how changes resulting from peripheral nerve injury may develop into chronic neuropathic pain through changes in the peripheral and central nervous system.

Cumulative effects of multiple pain sites in youth with chronic pain.

BACKGROUND: The experience of persistent pain in multiple locations is common in youth. Based on current literature, youth with multiple pain sites (MPS) are at risk of experiencing poorer emotional outcomes and a spread of symptoms into late adolescence and adulthood. Little is known regarding the association between MPS with physical and school functioning domains, particularly after initiation of multidisciplinary pain treatment. Therefore, the objective of this study was to examine the association of MPS with disability and school functioning among youth with chronic pain. METHODS: A total of 195 patients with chronic pain, aged 8-17, and their parents completed measures assessing patient distress and functioning at a multidisciplinary pain clinic evaluation and at 4-month follow-up. RESULTS: At evaluation, 63% of patients presented with MPS; 25% reporting MPS endorsed pain in five or more locations. When controlling for relevant demographic and emotional distress factors, MPS were associated with lower school functioning at evaluation with a persistent trend at follow-up. Although MPS were not a significant predictor of pain-related disability at evaluation, it emerged as significant at follow-up. CONCLUSIONS: Potentially due to the MPS load and the inverse effects that such a pain state has on function, such patients may be at risk for poorer health and school-related outcomes. The mechanisms influencing these relationships appear to extend beyond psychological/emotional factors and warrant further investigation in order to aid in our understanding of youth with MPS. SIGNIFICANCE: Youth with MPS may be at risk for experiencing poorer physical and school functioning in comparison with single-site peers, despite treatment initiation. Further research is warranted to inform assessment and treatment approaches for this subgroup of patients.

Validation of the German fear of pain questionnaire in a sample of children with mixed chronic pain conditions.

BACKGROUND: To date, no German instrument exists to measure pain-related fear in paediatric pain populations. The objective of the current study was to determine the construct validity of the translated German fear of pain questionnaire for children (GFOPQ-C) in a sample of children with mixed chronic pain disorders by testing the underlying factor structure, and its psychometric properties. METHOD: N = 241 children with mixed chronic pain disorders (aged 8-19 years) presenting to a specialized pain clinic completed the GFOPQ-C and several other pain, fear and disability measures. RESULTS: The two-factor structure of the FOPQ-C (fear, avoidance) was replicated. Internal consistency for the shortened German version was good for both subscales (Fear subscale: α = 0.89; avoidance subscale: α = 0.76). As expected, the fear subscale correlated highly with anxiety sensitivity (r = 0.63), pain catastrophizing (r = 0.62) and general anxiety (r = 0.54), while the avoidance subscale was more closely related to disability (r = 0.24) and school functioning (r = 0.28). Pain-related fear differed in children with chronic pain depending on their pain location with higher fear ratings in children with abdominal pain and musculoskeletal pain. CONCLUSION: The GFOPQ-C is a valid instrument that assesses two distinct dimensions of pain-related fear in children: fear and avoidance. Future research is needed to evaluate the impact of increased pain-related fear on outcomes over time as well as to examine pain-related fear among healthy children. This will enhance our knowledge of who might be particularly vulnerable to potentially dysfunctional trajectories, such as ongoing pain or anxiety symptoms. SIGNIFICANCE: The current study validates the first tool to assess pain-related fear in German-speaking children with chronic pain. Findings support two distinct domains: fear and activity avoidance.

Anxiety sensitivity and fear of pain in paediatric headache patients.

BACKGROUND: Recent research suggests that anxiety sensitivity (AS) may be a critical factor in the maintenance of chronic pain. Converging lines of evidence also propose a relationship between AS and fear of pain (FOP) that may result from interoceptive fear conditioning in interoceptively biased individuals. While some AS and FOP research has been carried out in adults, literature exploring this relationship is sparse in clinical paediatric populations. METHODS: This study investigated the hypotheses that FOP mediates the relationships between AS and disability as well as AS and somatization in children and adolescents with chronic headache pain. Mediation models were investigated using bootstrap regression analyses. RESULTS: Results indicate that the AS-disability relationship is mediated by FOP, whereas AS seems to contribute both directly and indirectly to somatization. CONCLUSION: These results provide evidence for the pivotal role of AS in the paediatric chronic pain model. The findings of this study further emphasize the application of the fear-avoidance model in children and provide new evidence for the critical role of AS in a paediatric headache population.

The responsive amygdala: treatment-induced alterations in functional connectivity in pediatric complex regional pain syndrome.

The amygdala is a key brain region with efferent and afferent neural connections that involve complex behaviors such as pain, reward, fear, and anxiety. This study evaluated resting state functional connectivity of the amygdala with cortical and subcortical regions in a group of chronic pain patients (pediatric complex regional pain syndrome) with age-sex matched control subjects before and after intensive physical-biobehavioral pain treatment. Our main findings include (1) enhanced functional connectivity from the amygdala to multiple cortical, subcortical, and cerebellar regions in patients compared with control subjects, with differences predominantly in the left amygdala in the pretreated condition (disease state); (2) dampened hyperconnectivity from the left amygdala to the motor cortex, parietal lobe, and cingulate cortex after intensive pain rehabilitation treatment within patients with nominal differences observed among healthy control subjects from time 1 to time 2 (treatment effects); (3) functional connectivity to several regions key to fear circuitry (prefrontal cortex, bilateral middle temporal lobe, bilateral cingulate, hippocampus) correlated with higher pain-related fear scores; and (4) decreases in pain-related fear associated with decreased connectivity between the amygdala and the motor and somatosensory cortex, cingulate, and frontal areas. Our data suggest that there are rapid changes in amygdala connectivity after an aggressive treatment program in children with chronic pain and intrinsic amygdala functional connectivity activity serving as a potential indicator of treatment response.

Psychological profiles distinguishing litigating and nonlitigating pain patients: subtle, and not so subtle.

Chronic pain patients in the midst of litigation over settlement for their injuries were examined as a naturally occurring group where one might expect various distortions or differences in test findings on the Minnesota Multiphasic Personality Inventory-Revised (MMPI-2). Similar groups of 43 chronic pain patients in litigation and 45 not in litigation were examined on 10 key MMPI-2 variables selected a priori. Multivariate analysis of variance revealed a significant difference between groups (p = .036). Litigators were most distinct in endorsing more obvious and fewer subtle symptoms. A conversion profile was also more salient for litigators once the obvious versus subtle differences were taken into account. Implications for use of the MMPI-2 and for clinical work with litigious patients are examined.