Pain
-
Chronic noncancer pain in children and adolescents can be impairing and results in substantial health care costs. Intensive interdisciplinary pain treatment (IIPT), an inpatient or day hospital treatment delivered by a team of 3 or more health professionals, may be an effective intervention for these children and adolescents. Based on previous reviews and meta-analyses, we updated findings regarding the description of available treatments and estimated the effectiveness of IIPT, overcoming methodological shortcomings of previous work by requesting and analyzing individual participant data. ⋯ Regarding treatment effectiveness, IIPT may result in large improvements in the mean pain intensity ( g = -1.28), disability ( g = -1.91), and number of missed school days at the 12-month follow-up ( g = -0.99), as well as moderate improvements in anxiety ( g = -0.77) and depression ( g = -0.76). The certainty of the evidence, however, was graded from very low to low. We recommend that future researchers use more scientific rigor to increase the certainty of the evidence for IIPT and standardize treatment outcomes for children and adolescents with chronic pain.
-
Trigeminal neuralgia (TN) is a rare but debilitating disorder characterized by excruciating facial pain, with a higher incidence in women. Recent studies demonstrated that TN patients present mutations in the gene encoding the Ca V 3.2 T-type calcium channel, an important player in peripheral pain pathways. We characterize the role of Ca V 3.2 channels in TN at 2 levels. ⋯ The effect of Z944 was absent in Ca V 3.2 -/- mice, indicating that Ca V 3.2 is the molecular target of the antihyperalgesic Z944 effect. Finally, enzyme-linked immunosorbent assay analysis revealed increased Ca V 3.2 channel expression in the spinal trigeminal subnucleus caudalis. Altogether, the present study demonstrates an important role of Ca V 3.2 channels in trigeminal pain.
-
Ample data support a prominent role of peripheral T-type calcium channels 3.2 (Ca V 3.2) in generating pain states. Development of primary sensory neuron-specific inhibitors of Ca V 3.2 channels is an opportunity for achieving effective analgesic therapeutics, but success has been elusive. Small peptides, especially those derived from natural proteins as inhibitory peptide aptamers (iPAs), can produce highly effective and selective blockade of specific nociceptive molecular pathways to reduce pain with minimal off-target effects. ⋯ Two prototype Ca V 3.2iPAs (iPA1 and iPA2) derived from the IDRs of Ca V 3.2 intracellular loops 2 and 3, respectively, were expressed selectively in the primary sensory neurons of dorsal root ganglia in vivo using recombinant adeno-associated virus (AAV), which produced sustained inhibition of calcium current conducted by Ca V 3.2/T-type channels and significantly attenuated both evoked and spontaneous pain behavior in rats with neuropathic pain after tibial nerve injury. Recordings from dissociated sensory neurons showed that AAV-mediated Ca V 3.2iPA expression suppressed neuronal excitability, suggesting that Ca V 3.2iPA treatment attenuated pain by reversal of injury-induced neuronal hypersensitivity. Collectively, our results indicate that Ca V 3.2iPAs are promising analgesic leads that, combined with AAV-mediated delivery in anatomically targeted sensory ganglia, have the potential to be a selective peripheral Ca V 3.2-targeting strategy for clinical treatment of pain.