SH2-B beta upregulates the expression of interleukin-1 beta in lung and visceral primary afferent neurons in asthmatic mice

A previous study by our research group showed that nerve growth factor is involved in the onset of asthma through regulating SH2-Bβ expression in the lung and visceral primary afferent neurons of asthmatic mice. This study sought to assess the expression level of interleukin-1β in primary afferent neurons in C7-T5 spinal ganglia, spinal cord and lung in asthmatic mice after blockage of SH2-Bβ. The levels of interleukin-1β protein in primary afferent neurons in the C7-T5 spinal ganglia and lung were decreased, and interleukin-1β mRNA expression also down-regulated in the spinal cord, medulla oblongata and lung tissue after blockage of SH2-Bβ. Our findings indicate that SH2-Bβ can upregulate the expression of interleukin-1β in C7-T5 spinal ganglia, spinal cord and lung of asthmatic mice.

Expression of gamma-aminobutyric acid type A receptor α_2 subunit in the dorsal root ganglion of rats with sciatic nerve injury

The γ-aminobutyric acid neurotransmitter in the spinal cord dorsal horn plays an important role in pain modulation through primary afferent-mediated presynaptic inhibition. The weakening of γ-aminobutyric acid-mediated presynaptic inhibition may be an important cause of neuropathic pain. γ-aminobutyric acid-mediated presynaptic inhibition is related to the current strength of γ-aminobutyric acid A receptor activation. In view of this, the whole-cell patch-clamp technique was used here to record the change in muscimol activated current of dorsal root ganglion neurons in a chronic constriction injury model. Results found that damage in rat dorsal root ganglion neurons following application of muscimol caused concentration-dependent activation of current, and compared with the sham group, its current strength and γ-aminobutyric acid A receptor protein expression decreased. Immunofluorescence revealed that γ-aminobutyric acid type A receptor α2 subunit protein expression decreased and was most obvious at 12 and 15 days after modeling. Our experimental findings confirmed that the y-aminobutyric acid type A receptor α2 subunit in the chronic constriction injury model rat dorsal root ganglion was downregulated, which may be one of the reasons for the reduction of injury in dorsal root ganglion neurons following muscimol-activated currents.

PLASMA EXTRAVASATION IN THE VISCERAL ORGANS CAUSED BY ELECTRICAL STIMULATION OF ACUPOINT "ZUSANLI" IN RATS

Objective To investigate the plasma extravasation of visceral organs caused by electrical stimulation of acupoint under the dorsal root reflex and axon reflex conditions. Methods By the means of measuring the content of Evans blue, this study investigated the plasma extravasation of visceral organs induced by electrical stimulation of acupoint 'Zusanli'(ST 36).Results The Evans blue content in the visceral organs such as liver, spleen, pancreas and the whole gastrointestinal tract in rats increased significantly after electrical stimulation of acupoint 'Zusanli' compared with that of the control group (P<0.01). The Evans blue extravasation in the above visceral organs was blocked by pre-treatment of capsaicin (66 mmol·L -1, 50 μL) into the acupoint. Conclusion The neurogenic inflammation of the visceral organs evoked by electrical stimulation of acupoint was mediated by the capsaicin-sensitive afferent fibers through the dorsal root reflex and axon reflex. It is a new method to study the correlation of meridian-viscera.

Neuronal Fc gamma receptor I as a novel mediator for IgG immune complex-induced peripheral sensitization

Chronic pain often accompanies immune-related diseases with an elevated level of IgG immune complex （IgG-IC） in the serum and/or the affected tissues though the underlying mechanisms are largely unknown. Fc gamma receptors （FcyRs）, known as the receptors for the Fc domain of immunoglobulin G （IgG）, are typically expressed on immune cells. A general consensus is that the activation of FcyRs by IgG-IC in such immune cells induces the release of proinflammatory cytokines from the immune cells, which may contribute to the IgG-IC-mediated peripheral sensitization. In addition to the immune cells, recent studies have revealed that FcyRI, but not FcyRII and FcyRIII, is also expressed in a subpopulation of primary sensory neurons. Moreover, IgG-IC directly excites the primary sensory neurons through neuronal FcyRI. These findings indicate that neuronal FcyRI provides a novel direct linkage between immunoglobulin and primary sensory neurons, which may be a novel target for the treatment of pain in the immune-related disorders. In this review, we summarize the expression pattern, functions, and the associated cellular signaling of FcyRs in the primary sensory neurons.

Responses of Primary Afferent Fibers to Acupuncture-Like Peripheral Stimulation at Different Frequencies:Characterization by Single-Unit Recording in Rats

The pain-relieving effect of acupuncture is known to involve primary afferent nerves(PANs) via their roles in signal transmission to the CNS.Using single-unit recording in rats,we characterized the generation and transmission of electrical signals in Aβ and Aδ fibers induced by acupuncture-like stimuli.Acupuncture-like signals were elicited in PANs using three techniques:manual acupuncture(MAc),emulated acupuncture(EAc),and electro-acupuncture(EA)-like peripheral electrical stimulation(PES).The discharges evoked by MAc and EAc were mostly in a burst pattern with average intra-burst and inter-burst firing rates of 90 Hz and 2 Hz,respectively.The frequency of discharges in PANs was correlated with the frequency of PES.The highest discharge frequency was 246 Hz in Aβ fibers and 180 Hz in Aδ fibers.Therefore,EA in a dense-disperse mode(at alternating frequency between 2 Hz and 15 Hz or between 2 Hz and 100 Hz) best mimics MAc.Frequencies of EA output>250 Hz appear to be obsolete for pain relief.

Differential Inhibition of Nav1.7 and Neuropathic Pain by Hybridoma-Produced and Recombinant Monoclonal Antibodies that Target Nav1.7

Abstract The voltage-gated Na＋ channel subtype Nav1.7 is important for pain and itch in rodents and humans. We previously showed that a Nav1.7-targeting monoclonal antibody （SVmab） reduces Na＋ currents and pain and itch responses in mice. Here, we investigated whether recom- binant SVmab （rSVmab） binds to and blocks Nav1.7 similar to SVmab. ELISA tests revealed that SVmab was capable of binding to Nav1.7-expressing HEK293 cells, mouse DRG neurons, human nerve tissue, and the voltagesensor domain II of Nav1.7. In contrast, rSVmab showed no or weak binding to Nav1.7 in these tests. Patch-clamp recordings showed that SVmab, but not rSVmab, markedly inhibited Na＋ currents in Nav1.7-expressing HEK293 cells. Notably, electrical field stimulation increased the blocking activity of SVmab and rSVmab in Nav1.7- expressing HEK293 cells. SVmab was more effective than rSVmab in inhibiting paclitaxel-induced mechanical allodynia. SVmab also bound to human DRG neurons and inhibited their Na＋ currents. Finally, potential reasons for the differential efficacy of SVmab and rSVmab and future directions are discussed.