Identifying local and descending inputs for primary sensory neurons

Zhang, Yi; Zhao, Shengli; Rodriguez, Erica; Takatoh, Jun; Han, Bao Xia; Zhou, Xiang; Wang, Fan

doi:10.1172/jci81156

Cited by 103 publications

(95 citation statements)

References 79 publications

(94 reference statements)

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“…Neurons within the rostral ventromedial medulla (RVM) are known to project to the spinal or medullary dorsal horns to directly or indirectly enhance or diminish nociceptive traffic [85]. We examined the possible contribution of the RVM in the GLED-induced antinociceptive response by microinjection of 2% lidocaine.…”

Section: Resultsmentioning

confidence: 99%

Long-lasting antinociceptive effects of green light in acute and chronic pain in rats

Ibrahim

Patwardhan

Gilbraith³

et al. 2016

Pain

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Treatments for chronic pain are inadequate, and new options are needed. Nonpharmaceutical approaches are especially attractive with many potential advantages including safety. Light therapy has been suggested to be beneficial in certain medical conditions such as depression, but this approach remains to be explored for modulation of pain. We investigated the effects of light-emitting diodes (LEDs), in the visible spectrum, on acute sensory thresholds in naive rats as well as in experimental neuropathic pain. Rats receiving green LED light (wavelength 525 nm, 8 h/d) showed significantly increased paw withdrawal latency to a noxious thermal stimulus; this antinociceptive effect persisted for 4 days after termination of last exposure without development of tolerance. No apparent side effects were noted and motor performance was not impaired. Despite LED exposure, opaque contact lenses prevented antinociception. Rats fitted with green contact lenses exposed to room light exhibited antinociception arguing for a role of the visual system. Antinociception was not due to stress/anxiety but likely due to increased enkephalins expression in the spinal cord. Naloxone reversed the antinociception, suggesting involvement of central opioid circuits. Rostral ventromedial medulla inactivation prevented expression of light-induced antinociception suggesting engagement of descending inhibition. Green LED exposure also reversed thermal and mechanical hyperalgesia in rats with spinal nerve ligation. Pharmacological and proteomic profiling of dorsal root ganglion neurons from green LED-exposed rats identified changes in calcium channel activity, including a decrease in the N-type (CaV2.2) channel, a primary analgesic target. Thus, green LED therapy may represent a novel, nonpharmacological approach for managing pain.

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Section: Resultsmentioning

confidence: 99%

Long-lasting antinociceptive effects of green light in acute and chronic pain in rats

Ibrahim

Patwardhan

Gilbraith³

et al. 2016

Pain

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“…It is also evident that SGCs in sympathetic ganglia play a role in the regulating the synaptic environment, and nonmyelinating Schwann cells can enhance synaptogenesis at the neuromuscular junction (Feng and Ko, 2008; Ullian et al, 2004). Recent studies also demonstrate that DRG neurons communicate with each other and with glia through release of various mediators, suggesting that DRG neuron somata also possess ‘presynaptic-like’ or ‘sandwich synapse’ features in intraganglionic neuron-SGC-neuron communications (Gu et al, 2010; Ren and Dubner, 2010; Rozanski et al, 2013; Zhang et al, 2015). The majority of cholesterol in the peripheral nervous system resides in myelin, and the role of cholesterol metabolism in Schwann cells has been well documented, particularly with regards to degeneration and regeneration of axons (Fu et al, 1998; Goodrum, 1990, 1993; Singer and Bryant, 1969).…”

Section: Discussionmentioning

confidence: 99%

HMG-CoA synthase isoenzymes 1 and 2 localize to satellite glial cells in dorsal root ganglia and are differentially regulated by peripheral nerve injury

et al. 2016

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In dorsal root ganglia (DRG), satellite glial cells (SGCs) tightly ensheathe the somata of primary sensory neurons to form functional sensory units. SGCs are identified by their flattened and irregular morphology and expression of a variety of specific marker proteins. In this report, we present evidence that the 3-hydroxy-3-methylglutaryl coenzyme A synthase isoenzymes 1 and 2 (HMGCS1 and HMGCS2) are abundantly expressed in SGCs. Immunolabeling with the validated antibodies revealed that both HMGCS1 and HMGCS2 are highly colabeled with a selection of SGC markers, including GS, GFAP, Kir4.1, GLAST1, GDNF, and S100 but not with microglial cell marker Iba1, myelin sheath marker MBP, and neuronal marker β3-tubulin or phosphorylated CaMKII. HMGCS1 but not HMGCS2 immunoreactivity in SGCs is reduced in the fifth lumbar (L5) DRGs that contain axotomized neurons following L5 spinal nerve ligation (SNL) in rats. Western blot showed that HMGCS1 protein level in axotomized L5 DRGs is reduced after SNL to 66 ± 8% at 3 days (p < 0.01, n=4 animals in each group) and 58 ± 13% at 28 days (p < 0.001, n=9 animals in each group) of its level in control samples, whereas HMGCS2 protein was comparable between injured and control DRGs. These results identify HMGCSs as the alternative markers for SGCs in DRGs. Downregulated HMGCS1 expression in DRGs after spinal nerve injury may reflect a potential role of abnormal sterol metabolism of SGCs in the nerve injured-induced neuropathic pain.

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“…FuGB2-coated lentiviruses containing Cre-N (RG-LV-Cre-N) and Cre-C (RG-LV-Cre-C) were produced and concentrated as described previously (Zhang et al, 2015). Briefly, HEK293T cells were transiently transfected with pLenti-hSynapsin-CreN or pLentihSynapsin-CreC together with psPAX2 and FuGB2 using polyethyleneimine "MAX" (PEI MAX) (Polysciences 24765).…”

Section: Methodsmentioning

confidence: 99%

“…AAV8-hsyn-Flex-GFP and AAV8-hSyn-Flex-TeNT-P2A-GFP viruses were generated and concentrated as described before (Zhang et al, 2015). In brief, HEK293T cells were transiently transfected with pAAV-hSynFlex-GFP or pAAV-hSyn-Flex-TeNT-P2A-GFP, together with AAV serotype plasmid AAV8, and pAd.DELTA F6 using PEI MAX (Polysciences 24765).…”

Section: Methodsmentioning

confidence: 99%

“…TeNT cleaves synaptobrevin proteins on synaptic vesicles and thereby silences the outputs of bilaterally projecting neurons (Yamamoto et al, 2003). To selectively silence BPNs, we injected RG-LV-Cre-N and RG-LV-Cre-C into the left and right trigeminal motor nucleus, respectively, and injected AAVFlex-TeNT-GFP (Zhang et al, 2015) that expressed Credependent TeNT and EGFP into the left and right Rt-MoVII (Fig. 4A).…”

Section: Progressive Silencing Of Subsets Of Bpns With Tent Increasesmentioning

confidence: 99%

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Supratrigeminal Bilaterally Projecting Neurons Maintain Basal Tone and Enable Bilateral Phasic Activation of Jaw-Closing Muscles

Stanek

Rodriguez

Zhao

et al. 2016

Journal of Neuroscience

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Anatomical studies have identified brainstem neurons that project bilaterally to left and right oromotor pools, which could potentially mediate bilateral muscle coordination. We use retrograde lentiviruses combined with a split-intein-mediated split-Cre-recombinase system in mice to isolate, characterize, and manipulate a population of neurons projecting to both the left and right jaw-closing trigeminal motoneurons. We find that these bilaterally projecting premotor neurons (BPNs) reside primarily in the supratrigeminal nucleus (SupV) and the parvicellular and intermediate reticular regions dorsal to the facial motor nucleus. These BPNs also project to multiple midbrain and brainstem targets implicated in orofacial sensorimotor control, and consist of a mix of glutamatergic, GABAergic, and glycinergic neurons, which can drive both excitatory and inhibitory inputs to trigeminal motoneurons when optogenetically activated in slice. Silencing BPNs with tetanus toxin light chain (TeNT) increases bilateral masseter activation during chewing, an effect driven by the expression of TeNT in SupV BPNs. Acute unilateral optogenetic inhibition of SupV BPNs identifies a group of tonically active neurons that function to lower masseter muscle tone, whereas unilateral optogenetic activation of SupV BPNs is sufficient to induce bilateral masseter activation both during resting state and during chewing. These results provide evidence for SupV BPNs in tonically modulating jawclosing muscle tone and in mediating bilateral jaw closing.

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Identifying local and descending inputs for primary sensory neurons

Cited by 103 publications

References 79 publications

Long-lasting antinociceptive effects of green light in acute and chronic pain in rats

Long-lasting antinociceptive effects of green light in acute and chronic pain in rats

HMG-CoA synthase isoenzymes 1 and 2 localize to satellite glial cells in dorsal root ganglia and are differentially regulated by peripheral nerve injury

Supratrigeminal Bilaterally Projecting Neurons Maintain Basal Tone and Enable Bilateral Phasic Activation of Jaw-Closing Muscles

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