Methylglyoxal activates transient receptor potential A1/V1 via reactive oxygen species in the spinal dorsal horn.

Methylglyoxal (MGO), a highly reactive dicarbonyl metabolite of glucose primarily formed during the glycolytic pathway, is a precursor of advanced glycation end-products (AGEs). Recently, numerous studies have shown that MGO accumulation can cause pain and hyperalgesia. However, the mechanism through which MGO induces pain in the spinal dorsal horn remains unclear. The present study investigated the effect of MGO on spontaneous excitatory postsynaptic currents (sEPSC) in rat spinal dorsal horn neurons using blind whole-cell patch-clamp recording. Perfusion of MGO increased the frequency and amplitude of sEPSC in spinal horn neurons in a concentration-dependent manner. Additionally, MGO administration increased the number of miniature EPSC (mEPSC) in the presence of tetrodotoxin, a sodium channel blocker. However, 6-cyano-7-nitroqiunocaline-2,3-dione (CNQX), an AMPA/kainate receptor antagonist, blocked the enhancement of sEPSC by MGO. HC-030031, a TRP ankyrin-1 (TRPA1) antagonist, and capsazepine, a TRP vanilloid-1 (TRPV1) antagonist, inhibited the action of MGO. Notably, the effects of MGO were completely inhibited by HC-030031 and capsazepine. MGO generates reactive oxygen species (ROS) via AGEs. ROS also potentially induce pain via TRPA1 and TRPV1 in the spinal dorsal horn. Furthermore, we examined the effect of MGO in the presence of N-tert-butyl-α-phenylnitrone (PBN), a non-selective ROS scavenger, and found that the effect of MGO was completely inhibited. These results suggest that MGO increases spontaneous glutamate release from the presynaptic terminal to spinal dorsal horn neurons through TRPA1, TRPV1, and ROS and could enhance excitatory synaptic transmission.

Intraforaminal cervical gas cyst with vacuum disc treated by anterior cervical discectomy and fusion: illustrative case.

BACKGROUND: The authors report an extremely rare presentation of a patient with an intraforaminal cervical gas cyst with radiculopathy. The patient's condition was refractory to conservative treatment, and he was treated by anterior cervical discectomy and fusion (ACDF). Several intraspinal gas cysts with lumbar disc herniation have been treated surgically. However, no cases of intraforaminal cervical gas requiring ACDF have been reported. OBSERVATIONS: A 70-year-old male patient presented with right-sided neck and shoulder pain, aggravating in the supine position. Cervical radiography showed vacuum disc phenomenon at C4-5, and multiplanar computed tomography showed intraforaminal gas along the right C5 nerve root. The patient experienced severe pain with impaired sleep and daytime fatigue. After confirming C5 radiculopathy using an echo-guided technique using ultrasonography guidance, the authors performed C4-5 ACDF. Postoperatively, the patient's neck and shoulder pain disappeared immediately. There was no recurrence at the 2-year follow-up. LESSONS: This is the first case report of an intraspinal cervical gas cyst with radiculopathy treated by ACDF surgery. The vacuum disc had been implicated as the genesis of the intraforaminal cervical gas cyst, leading to radiculopathy. ACDF surgery provides favorable outcomes in cases of intraspinal gas refractory to conservative therapy.

11B NMR sensing of d-block metal ions in vitro and in cells based on the carbon-boron bond cleavage of phenylboronic acid-pendant cyclen (cyclen = 1,4,7,10-tetraazacyclododecane).

Noninvasive magnetic resonance imaging (MRI) including the "chemical shift imaging (CSI)" technique based on (1)H NMR signals is a powerful method for the in vivo imaging of intracellular molecules and for monitoring various biological events. However, it has the drawback of low resolution because of background signals from intrinsic water protons. On the other hand, it is assumed that the (11)B NMR signals which can be applied to a CSI technique have certain advantages, since boron is an ultratrace element in animal cells and tissues. In this manuscript, we report on the sensing of biologically indispensable d-block metal cations such as zinc, copper, iron, cobalt, manganese, and nickel based on (11)B NMR signals of simple phenylboronic acid-pendant cyclen (cyclen = 1,4,7,10-tetraazacyclododecane), L(6) and L(7), in aqueous solution at physiological pH. The results indicate that the carbon-boron bond of L(6) is cleaved upon the addition of Zn(2+) and the broad (11)B NMR signal of L(6) at 31 ppm is shifted upfield to 19 ppm, which corresponds to the signal of B(OH)(3). (1)H NMR, X-ray single crystal structure analysis, and UV absorption spectra also provide support for the carbon-boron bond cleavage of ZnL(6). Because the cellular uptake of L(6) was very small, a more cell-membrane permeable ligand containing the boronic acid ester L(7) was synthesized and investigated for the sensing of d-block metal ions using (11)B NMR. Data on (11)B NMR sensing of Zn(2+) in Jurkat T cells using L(7) is also presented.