Pain
-
Children born very prematurely (< or =32 weeks) often exhibit visual-perceptual difficulties at school-age, even in the absence of major neurological impairment. The alterations in functional brain activity that give rise to such problems, as well as the relationship between adverse neonatal experience and neurodevelopment, remain poorly understood. Repeated procedural pain-related stress during neonatal intensive care has been proposed to contribute to altered neurocognitive development in these children. ⋯ We demonstrated alterations in the spectral structure of spontaneous cortical oscillatory activity in ELGA children at school-age. Cumulative neonatal pain-related stress was associated with changes in background cortical rhythmicity in these children, and these alterations in spontaneous brain oscillations were negatively correlated with visual-perceptual abilities at school-age, and were not driven by potentially confounding neonatal variables. These findings provide the first evidence linking neonatal pain-related stress, the development of functional brain activity, and school-age cognitive outcome in these vulnerable children.
-
Randomized Controlled Trial
Longstanding neuropathic pain after spinal cord injury is refractory to transcranial direct current stimulation: A randomized controlled trial.
Neuropathic pain remains one of the most difficult consequences of spinal cord injury (SCI) to manage. It is a major cause of suffering and adds to the physical, emotional, and societal impact of the injury. Despite the use of the best available treatments, two thirds of people experiencing neuropathic pain after SCI do not achieve satisfactory pain relief. ⋯ A similar lack of effect was also seen after sham treatment. Because the injury duration in this study was significantly greater than that of previous investigations, it is possible that tDCS is an effective analgesic only in individuals with relatively recent injuries and pain. Future investigations comparing a range of injury durations are required if we are to determine whether this is indeed the case.
-
Growth factors such as nerve growth factor and glial cell line-derived neurotrophic factor are known to induce pain sensitization. However, a plethora of other growth factors is released during inflammation and tissue regeneration, and many of them are essential for wound healing. Which wound-healing factors also alter the sensitivity of nociceptive neurons is not well known. We studied the wound-healing factor, basic fibroblast growth factor (bFGF), for its role in pain sensitization. Reverse transcription polymerase chain reaction showed that the receptor of bFGF, FGFR1, is expressed in lumbar rat dorsal root ganglia (DRG). We demonstrated presence of FGFR1 protein in DRG neurons by a recently introduced quantitative automated immunofluorescent microscopic technique. FGFR1 was expressed in all lumbar DRG neurons as quantified by mixture modeling. Corroborating the mRNA and protein expression data, bFGF induced Erk1/2 phosphorylation in nociceptive neurons, which could be blocked by inhibition of FGF receptors. Furthermore, bFGF activated Erk1/2 in a dose- and time-dependent manner. Using single-cell electrophysiological recordings, we found that bFGF treatment of DRG neurons increased the current-density of NaV1.8 channels. Erk1/2 inhibitors abrogated this increase. Importantly, intradermal injection of bFGF in rats induced Erk1/2-dependent mechanical hyperalgesia. ⋯ Analyzing intracellular signaling dynamics in nociceptive neurons has proven to be a powerful approach to identify novel modulators of pain. In addition to describing a new sensitizing factor, our findings indicate the potential to investigate wound-healing factors for their role in nociception.
-
Randomized Controlled Trial
Efficacy, safety, and tolerability of fulranumab, an anti-nerve growth factor antibody, in the treatment of patients with moderate to severe osteoarthritis pain.
Nerve growth factor (NGF) is increased in chronic pain conditions. This study examined analgesic efficacy and safety of fulranumab, a fully human monoclonal anti-NGF antibody, in adults with chronic osteoarthritis pain. Patients (n=466, intent-to-treat) were randomized to receive, in addition to their current pain therapy, subcutaneous injections in 1 of 6 parallel treatment groups: placebo (n=78), fulranumab 1 mg (n=77) or 3 mg (n=79) every 4 weeks (Q4wk), 3 mg (n=76), 6 mg (n=78), or 10 mg (n=78) every 8 weeks (Q8wk). ⋯ Most neurologic-related treatment-emergent adverse events were mild or moderate and resolved at the end of week 12. Serious adverse events occurred in 3 patients, but they were not neurologically related and resolved before study completion. Fulranumab treatment resulted in statistically significant efficacy in pain measures and physical function versus placebo and was generally well tolerated.