Regulation of axonal regeneration following spinal cord injury in the lamprey.

Following rostral spinal cord injury (SCI) in larval lampreys, injured descending brain neurons, particularly reticulospinal (RS) neurons, regenerate their axons, and locomotor behavior recovers in a few weeks. However, axonal regeneration of descending brain neurons is mostly limited to relatively short distances, but the mechanisms for incomplete axonal regeneration are unclear. First, lampreys with rostral SCI exhibited greater axonal regeneration of descending brain neurons, including RS neurons, as well as more rapid recovery of locomotor muscle activity right below the lesion site, compared with animals with caudal SCI. In addition, following rostral SCI, most injured RS neurons displayed the "injury phenotype," whereas following caudal SCI, most injured neurons displayed normal electrical properties. Second, following rostral SCI, at cold temperatures (~4-5°C), axonal transport was suppressed, axonal regeneration and behavioral recovery were blocked, and injured RS neurons displayed normal electrical properties. Cold temperatures appear to prevent injured RS neurons from detecting and/or responding to SCI. It is hypothesized that following rostral SCI, injured descending brain neurons are strongly stimulated to regenerate their axons, presumably because of elimination of spinal synapses and reduced neurotrophic support. However, when these neurons regenerate their axons and make synapses right below the lesion site, restoration of neurotrophic support very likely suppress further axonal regeneration. In contrast, caudal SCI is a weak stimulus for axonal regeneration, presumably because of spared synapses above the lesion site. These results may have implications for mammalian SCI, which can spare synapses above the lesion site for supraspinal descending neurons and propriospinal neurons.NEW & NOTEWORTHY Lampreys with rostral spinal cord injury (SCI) exhibited greater axonal regeneration of descending brain neurons and more rapid recovery of locomotor muscle activity below the lesion site compared with animals with caudal SCI. In addition, following rostral SCI, most injured reticulospinal (RS) neurons displayed the "injury phenotype," whereas following caudal SCI, most injured neurons had normal electrical properties. We hypothesize that following caudal SCI, the spared synapses of injured RS neurons might limit axonal regeneration and behavioral recovery.

Medical Judgments Across the Range of Reported Pain Severity: Clinician and Lay Perspectives.

BACKGROUND: While increasing evidence suggests that observers discount high-severity chronic pain, factors that occasion such discounting are poorly understood, particularly regarding health provider vs lay perspectives. OBJECTIVE: This study examined the effects of supporting medical evidence and comorbid psychological distress (pain behavior) on medical student and lay clinical judgments of increasingly severe patient pain reports. DESIGN: In a 2 × 2 × 2 × (7) mixed between- and within-subject design, participants (medical students vs lay) made clinical judgments after reading vignettes describing a hypothetical patient that varied in levels of medical evidence and pain behavior (low vs high) and pain severity (4/10-10/10). SUBJECTS: Fourth-year medical students (N = 115) and lay persons in the community (N = 300) participated in this research. RESULTS: While both medical student and lay judgments plateaued at high levels of pain severity, judgments regarding cause (medical vs psychological), treatment (opioid prescription), and disability showed growing divergence as levels of reported pain severity increased. Divergence relative to medical and psychological causes of pain was found irrespective of the level of supporting medical evidence; divergence relative to opioid treatment and support for a disability claim was found when supporting medical evidence was low. CONCLUSIONS: The results indicate differing expectations of chronic pain treatment for health care providers relative to the lay public that could impact clinical care, especially at high pain severity levels, where lay expectations diverge significantly from those of health professionals.