Histone deacetylase inhibition inhibits brachial plexus avulsion-induced neuropathic pain.

INTRODUCTION: Neuropathic pain induced by brachial plexus avulsion (BPA) is a pathological condition. We hypothesized that inhibition of histone deacetylase (HDAC) could suppress BPA-induced neuropathic pain through inhibition of transient reception potential (TRP) overexpression and protein kinase B (Akt)-mediated mammalian target of rapamycin (mTOR) activation. METHODS: We generated a rat BPA model; administered HDAC inhibitor tricostatin A (TSA) for 7 days postsurgery; and assessed the effects on HDAC expression, Akt phosphorylation, neuroinflammation, and mTOR activation. RESULTS: TSA treatment alleviated BPA-induced mechanical hyperalgesia, suppressed Akt phosphorylation, and increased HDAC. We found suppressed proinflammatory cytokine levels, TRPV1 and TRPM8 expression, and mTOR activity in TSA-treated BPA rats. DISCUSSION: Our results suggest that altered HDAC and Akt signaling are involved in BPA-induced neuropathic pain and that inhibition of HDAC could be an effective therapeutic approach in reducing neuropathic pain. Muscle Nerve 58: 434-440, 2018.

Experimental study on mechanical vibration massage for treatment of brachial plexus injury in rats.

OBJECTIVE: To investigate the curative effect of the self-made mechanical vibration massage instrument for treatment of brachial plexus injury in rats and to explore its mechanism. METHODS: Brachial plexus injury models were made in 144 Wistar rats and one week after natural healing of the wound, they were randomly divided into 3 groups, mechanical vibration treatment group (MV group), nerve growth factor treatment group (NGF group) and model group, 48 rats in each group. Then again, the each group was randomly divided into 4 subgroups, 7-day group, 14-day group, 21-day group and 28-day group, 12 rats in each subgroup. The MV group were treated by mechanical vibration at acupoints on three-yang and three-yin channels of the hand with the mechanical vibration massage instrument; The NGF group were treated with injection of NGF into musculus pectoralis major on the affected side; And the model group were normally fed with no treatment. After treatment for 7, 14, 21 and 28 days, the diameter of both forelimbs were measured, the electrophysiological examination on the brachial plexus in vitro and the ultrastructure observation with electron microscope on the affected side were carried out, the motor nerve conduction velocity (MNCV) and motor nerve action potential (MNAP) of the brachial plexus on the affected side, NGF content of submaxillary gland as well as muscular Na+, K(+)-ATPase activity were determined respectively. RESULTS: The different rates of the forelimb diameter in the MV group and the NGV group on the 14th d, 21st d and 28th d were better than those in the model group (P < 0.05 or P < 0.001), and in the MV group were better than those in the NGF group on the 21st d and the 28th d (P < 0.05). MNCV in the MV group and the NGV group on the 21st d and 28th d was better than that in the model group (P < 0.05 or P < 0.001), and in the MV group was better than that in the NGF group on the 28th d (P < 0.05). MNAP in the MV group and the NGV group on the 14th d, 21st d and 28th d was better than that in the model group (P < 0.05 or P < 0.001), and in the MV group was better than that in the NGF group on the 21st d and 28th d (P < 0.05). The NGF mean gray index of submaxillary gland in the model group was higher than that in the MV group and the NGF group on the 7th d (P < 0.05); in the NGF group and the model group was higher than that in the MV group on the 14th d (P < 0.05); and in the NGF group and the MV group was higher than that in the model group on the 21st d and 28th d (P < 0.05). Na+, K(+)-ATPase activity in the model group and the MV group was higher than that in the NGF group (P < 0.05) on the 14th d, and in the MV group was higher than that in the model group on the 28th d (P < 0.05). CONCLUSION: As compared with the NGF group and the model group, mechanical vibration treatment can effectively accelerate repair of injured brachial plexus, slow down atrophy of skeletal muscle, and promote secretion of NGF in submaxillary gland.

Peripheral nerve induces macrophage neurotrophic activities: regulation of neuronal process outgrowth, intracellular signaling and synaptic function.

Rat cortical neurons cultured in conditioned media from human monocyte-derived macrophages (MDM) show increased neuronal protein synthesis, neurite outgrowth, mitogen-activating protein kinase activity, and synaptic function. Neurotrophic properties of human MDM-conditioned media are significantly enhanced by human peripheral nerve and to a more limited extent by CD40 ligand pre-stimulation. Such positive effects of MDM secretions on neuronal function parallel the secretion of brain-derived neurotrophic factor (BDNF). MDM activation cues may serve to balance toxic activities produced during neurodegenerative diseases and thus, under certain circumstances, mitigate neuronal degeneration.

Membrane peptidases in the peripheral nervous system of the pig: their localization by immunohistochemistry at light and electron microscopic levels.

The presence and cellular localization of five membrane peptidases has been investigated in peripheral nerves, including those of the autonomic nervous system, in the pig. Endopeptidase-24.11 ("enkephalinase") peptidyl dipeptidase A, aminopeptidase N, aminopeptidase W and dipeptidyl peptidase IV were studied by both enzymic assays of membranes prepared from samples of nerve and by immunoperoxidase histochemistry at light and in two cases, endopeptidase-24.11 and aminopeptidase W, at electron microscopic levels. All five peptidases could be quantified by enzymic assay, though the activities were about 1% of those in renal microvilli and less than those of choroid plexus membranes. Endopeptidase-24.11 was associated with Schwann cell membranes in all types of nerve examined, including major nerves containing predominantly myelinated fibres as well as autonomic nerves, such as the vagus and splenic nerves and the sympathetic chain, staining being observed in membranes associated with myelinated and unmyelinated fibres. The Schwann cell location of endopeptidase-24.11 was confirmed by correlation with immunostaining for glial fibrillary acidic protein and by electron microscopy. This peptidase is known to have a wide repertoire of susceptible substrates among neuropeptides which was here shown to include vasoactive intestinal polypeptide (Km 268 microM, kcat 568 min-1), one of a number of neuropeptides present in peripheral nerve fibres. Three of the peptidases, peptidyl dipeptidase A, aminopeptidase N and dipeptidyl peptidase IV, were associated with microvessels of peripheral nerves. Aminopeptidase N was also observed in connective tissue elements, including the perineurium. Aminopeptidase W was unique among the five peptidases in having a neuronal localization. This was observed in unmyelinated and myelinated nerves and was supported by comparison with the pattern of staining observed for neurofilament protein and by electron microscopic immunoperoxidase staining. This observation was unexpected since aminopeptidase W has not been detected as a neuronal marker in the brain. Some possible roles for the membrane peptidases in peripheral nerves are discussed.

Expression of cytochrome P4501b1 (Cyp1b1) during early murine development.

PURPOSE: To examine the embryonic expression of cytochrome P4501b1 (Cyp1b1) gene by whole mount in situ hybridization. METHODS: FVB/NcrlBR mouse embryos staged at 9.5, 10.5, and 11.5 dpc were obtained by timed breeding experiments. Antisense and sense RNA probes labeled with digoxigenin UTP were generated by in vitro transcription of an 848 bp Cyp1b1 cDNA fragment that was subcloned into transcription vector pCRII-TOPO. The digoxigenin labeled RNA was localized using an alkaline phosphatase conjugated anti-digoxigenin Fab fragment. Colorimetric detection of the digoxigenin labeled probe was performed with substrate solution containing 4-nitro-blue tetrazolium chloride (NBT) and 5-bromo-4-chloro-3-indolyl phosphate (BCIP). RESULTS: During early stages of murine development Cyp1b1 mRNA was detected in the developing eye, hindbrain, branchial arches, forelimb bud, ligaments supporting the liver primordium and developing kidney. In the eye and forelimb bud Cyp1b1 displayed restricted expression along the axes of development. In the developing eye Cyp1b1 exhibited dorsal expression with respect to the dorso-distal/proximo-ventral axis and anterior expression with respect to the anterior-nasal/posterior-temporal axis. In the forelimb bud Cyp1b1 expression was localized posteriorly. The polarity of Cyp1b1 expression was lost at 11.5 dpc, at which time expression was additionally seen in ventral (eye) and anterior (forelimb bud) areas. CONCLUSIONS: The spatio-temporal expression patterns observed in this study suggest that during early stages of murine development, Cyp1b1 participates in establishment and/or maintenance of polarity along the axes of embryonic development. Expression of Cyp1b1 in the dorso-distal end of the optic cup, from which the ciliary body and iris are derived, correlates with the expression patterns seen in adult tissues and the abnormal development of these structures as part of the glaucoma phenotypes resulting from Cyp1b1 mutations.

Choline acetyltransferase activity and evoked spinal cord potentials for diagnosis of brachial plexus injury.

The purpose of this study is to investigate the diagnostic value of evoked spinal cord potentials (ESCPs) and choline acetyltransferase (CAT) activity during exploration of injuries to the brachial plexus. We assessed 25 spinal roots in 19 patients. The results of the two investigations were consistent in all except two roots. Although assessment of ESCPs is easy and quick, it mainly records the nerve potentials along the sensory pathway. Although measurement of CAT activity needs a specimen of the nerve and the availability of a radioisotope laboratory, it gives direct information regarding the motor function of ventral spinal roots. These two techniques should be complementary to each other in order to achieve a more accurate diagnosis.

[Effect of the heat shock protein 27 on NOS expression of spinal cord anterior hornmotoneurons after brachial plexus avulsion].

AIM: To observe the effect of heat shock protein 27 (Hsp27) on nitric oxide synthase (NOS) of spinal cord anterior horn after brachial plexus roots avulsion. METHODS: Sixty male adult Wistar rats were divided into control and experiment groups at random. The experiment group subjected to heat shock under 45 degrees C for 15 min, and maintained under 42 degrees C for 20 min subsequently. After recovering 24 h under the room temperature, the nerves of brachial plexus were avulsion with microhemostatic forcep. In a span from 12 h to 7 d, these animals were killed at different time. But the control group only received the surgery of the nerve roots of brachial plexus avulsion. The freeze sections of spinal cord were stained by NADPH-d histochemistry, HSP27 immunohistochemical. RESULTS: (1) In experiment group, the motoneuron began to express NOS abundantly at 12 h after avulsion (A=0.13625). Then the NOS-positive neurons declined quickly, but in control group, the motoneuron began to express NOS at the 5th day after lesion. (2) Hsp27 begin to show the peak at 1 d in experiment and control groups, but the experiment group were more strong than the control group. CONCLUSION: Hsp27 inhibited NOS of motoneuron after avulsion and brought into full play the cytoprotection.

Inhibiting parabrachial fatty acid amide hydrolase activity selectively increases the intake of palatable food via cannabinoid CB1 receptors.

These studies investigated feeding responses to indirect activation of parabrachial cannabinoid CB1 receptors. Arachidonoyl serotonin (AA5HT), an inhibitor of the endocannabinoid degradative enzyme, fatty acid amide hydrolase (FAAH), was infused into the parabrachial nucleus of male Sprague-Dawley rats, and intakes of high-fat/sucrose pellets and standard rodent chow were subsequently evaluated under various feeding schedules. FAAH blockade stimulated the intake of high-fat/sucrose pellets that were presented daily for 4 h during the light period, with compensatory decreases in the consumption of standard chow during the ensuing 20 h. These diet-selective changes were repeated on the next day, indicating a shift in feeding toward the more palatable diet that lasted for 48 h after a single infusion. The cannabinoid CB1 receptor antagonist, AM251, blocked the orexigenic actions of AA5HT, implicating CB1 receptors in mediating the feeding responses to FAAH inactivation. When the feeding schedule was reversed, AA5HT produced nominal increases in the consumption of standard chow for the 4-h access period, but substantial increases in the intake of high-fat/sucrose during the following 20-h interval. When presented with only high-fat/sucrose diet for 24 h, AA5HT increased 24-h food intake. In contrast, when given 24-h access only to standard chow, AA5HT failed to affect intake. Therefore, indirectly activating parabrachial CB1 receptors by blocking the degradation of native ligands selectively stimulates the intake of palatable food, with differential actions on total energy intake depending upon the feeding schedule. Our results support a role for parabrachial cannabinoid mechanisms in providing physiological regulation to neural substrates modulating feeding, energy balance, and behavioral responses for natural reward.