Pain
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Spinal projection neurons convey nociceptive signals to multiple brain regions including the parabrachial (PB) nucleus, which contributes to the emotional valence of pain perception. Despite the clear importance of projection neurons to pain processing, our understanding of the factors that shape their intrinsic membrane excitability remains limited. Here, we investigate a potential role for the Na leak channel NALCN in regulating the activity of spino-PB neurons in the developing rodent. ⋯ In addition, substance P (SP) activated INALCN in ascending projection neurons through downstream Src kinase signaling, and the knockout of NALCN prevented SP-evoked action potential discharge in this neuronal population. These results identify, for the first time, NALCN as a strong regulator of neuronal activity within central pain circuits and also elucidate an additional ionic mechanism by which SP can modulate spinal nociceptive processing. Collectively, these findings indicate that the level of NALCN conductance within spino-PB neurons tightly governs ascending nociceptive transmission to the brain and thereby potentially influences pain perception.
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Randomized Controlled Trial
Efficacy of hypnosis on pain, wound-healing, anxiety, and stress in children with acute burn injuries: a randomized controlled trial.
No randomized controlled trial has investigated the efficacy of hypnosis for reducing pain and improving wound-healing in children with burns. This randomized controlled trial aimed to investigate whether hypnosis decreases pain, anxiety, and stress and accelerates wound-healing in children undergoing burn wound procedures. Children (4-16 years) with acute burns presenting for their first dressing change were randomly assigned to a Hypnosis Group who received hypnosis plus standard care or a Standard Care Group who received standard pharmacological and nonpharmacological intervention. ⋯ An effect on the primary outcomes of pain and wound healing was not supported {self-reported pain intensity largest Mean Difference [MD] = -0.85 (95% confidence interval [CI]: -1.91 to 0.22), P = 0.12; MD for re-epithelialization = -0.46 [95% CI: -4.27 to 3.35], P = 0.81}. Some support was found for an effect on the secondary outcomes of preprocedural anxiety (MD = -0.80 [95% CI: -1.50 to -0.10], P = 0.03 before the second dressing change) and heart rate as a measure of stress (MD = -15.20 [-27.20 to -3.20], P = 0.01 and MD = -15.39 [-28.25 to -2.53], P = 0.02 before and after the third dressing change). Hypnosis may be effective for decreasing preprocedural anxiety and heart rate in children undergoing repeated pediatric wound care procedures but not for reducing pain intensity or accelerating wound healing.
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Randomized Controlled Trial Multicenter Study
A randomised, placebo-controlled clinical trial with the α2/3/5 subunit selective GABAA positive allosteric modulator PF-06372865 in patients with chronic low back pain.
The effect of PF-06372865, a subtype-selective positive allosteric modulator of the γ-aminobutyric acid type A (GABAA) receptor, on chronic low back pain was investigated in a randomised, placebo- and active-controlled phase 2 clinical trial. The parallel treatment group trial consisted of a 1-week single-blind placebo run in the phase, followed by 4-week double-blind treatment. Patients were randomised to receive either PF-06372865, naproxen, or placebo twice a day for 4 weeks. ⋯ PF-06372865 was well tolerated. The most common treatment-related adverse events in the PF-06372865 arm were somnolence (5 mild and 4 moderate), dizziness (2 mild and 3 moderate), and nausea (2 mild). Although the reason for the lack of analgesic effect is not completely clear, it may be a result of not achieving sufficient receptor occupancy to drive efficacy.
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Pontine noradrenergic neurones form part of a descending inhibitory system that influences spinal nociceptive processing. Weak or absent descending inhibition is a common feature of chronic pain patients. We examined the extent to which the descending noradrenergic system is tonically active, how control of spinal neuronal excitability is integrated into thalamic relays within sensory-discriminative projection pathways, and how this inhibitory control is altered after nerve injury. ⋯ These data suggest descending noradrenergic inhibitory pathways are tonically active in sham rats. Moreover, in neuropathic states, descending inhibitory control is diminished, but not completely absent, and distinguishes between spontaneous and evoked neuronal activity. These observations may have implications for how analgesics targeting the noradrenergic system provide relief.