High prevalence of carpal tunnel syndrome in individuals with rare nerve growth factor-beta mutation.

In Sweden, a large family with a point mutation in the nerve growth factor-beta gene has previously been identified. The carriers of this mutation have reduced small-fibre density and selective deficits in deep pain and temperature modalities. The clinical findings in this population are described as hereditary sensory and autonomic neuropathy type V. The purpose of the current study was to investigate the prevalence of carpal tunnel syndrome in hereditary sensory and autonomic neuropathy type V based on clinical examinations and electrophysiological measurements. Furthermore, the cross-sectional area of the median nerve at the carpal tunnel inlet was measured with ultrasonography. Out of 52 known individuals heterozygous for the nerve growth factor-beta mutation in Sweden, 23 participated in the current study (12 males, 11 females; mean age 55 years; range 25-86 years). All participants answered a health questionnaire and underwent clinical examination followed by median nerve conduction study in a case-control design, and measurement of the nerve cross-sectional area with ultrasonography. The diagnosis of carpal tunnel syndrome was made based on consensus criteria using patient history and nerve conduction study. The prevalence of carpal tunnel syndrome in the hereditary sensory and autonomic neuropathy group was 35% or 52% depending on whether those individuals who had classic symptoms of carpal tunnel syndrome but negative nerve conduction studies were included or not. Those who had a high likelihood of carpal tunnel syndrome based on classic/probable patient history with positive nerve conduction study had a significantly larger median nerve cross-sectional area than those who had an unlikely patient history with negative nerve conduction study. The prevalence of carpal tunnel syndrome was 10-25 times higher in individuals heterozygous for the nerve growth factor-beta mutation than the general Swedish population. Further studies are needed to better understand the underlying pathophysiological mechanisms.

An ultrafast system for signaling mechanical pain in human skin.

The canonical view is that touch is signaled by fast-conducting, thickly myelinated afferents, whereas pain is signaled by slow-conducting, thinly myelinated ("fast" pain) or unmyelinated ("slow" pain) afferents. While other mammals have thickly myelinated afferents signaling pain (ultrafast nociceptors), these have not been demonstrated in humans. Here, we performed single-unit axonal recordings (microneurography) from cutaneous mechanoreceptive afferents in healthy participants. We identified A-fiber high-threshold mechanoreceptors (A-HTMRs) that were insensitive to gentle touch, encoded noxious skin indentations, and displayed conduction velocities similar to A-fiber low-threshold mechanoreceptors. Intraneural electrical stimulation of single ultrafast A-HTMRs evoked painful percepts. Testing in patients with selective deafferentation revealed impaired pain judgments to graded mechanical stimuli only when thickly myelinated fibers were absent. This function was preserved in patients with a loss-of-function mutation in mechanotransduction channel PIEZO2. These findings demonstrate that human mechanical pain does not require PIEZO2 and can be signaled by fast-conducting, thickly myelinated afferents.

Brilliant blue G treatment facilitates regeneration after optic nerve injury in the adult rat.

Injuries to the adult mammalian visual system often lead to functional deficits with little or no chance of spontaneous recovery. Previous studies in rats have demonstrated beneficial effects of inhibition of the P2X7 receptor with brilliant blue G (BBG) after spinal cord injury; however, little is known about BBG as a potential treatment strategy for optic nerve injuries. Adult Sprague-Dawley rats were subjected to a controlled optic nerve crush lesion and randomized to treatment with BBG (50 mg/kg body weight intravenously) or vehicle for 2 days after injury. The temporal pattern of axonal breakdown and regeneration, as well as formation of the glial scar and microglia/macrophage activation, was studied at 7, 14, and 28 days after lesion induction by immunohistochemical analysis. Results show reduced glial scar formation, less macrophage activation, and signs indicative of axonal regeneration beyond the glial scar in treated animals. No significant side effects from the treatment were observed. Effects on axonal breakdown, regeneration, and glial scar formation are discussed in relation to the proposed beneficial effects of BBG treatment. The present study demonstrates positive effects of BBG treatment on neural repair after traumatic optic nerve injury, and also shows its feasibility as a proposed future clinical treatment strategy.