Activation of ventrolateral orbital cortex improves mouse neuropathic pain–induced anxiodepression

An orbitofrontal cortex to midbrain projection modulates hypersensitivity after peripheral nerve injury

“…Furthermore, although we could not detect changes in the excitability of overall vlOFC glutamatergic neurons under current clamp, in neurons that project to the vlPAG, we observed in the balance between inhibitory and excitatory inputs an SNIinduced change toward more inhibition. We reiterate here that vlOFC pyramidal neuronal activity is decreased in a model of trigeminal neuropathic pain (Sheng et al, 2020). Collectively, we thus propose a model in which nerve-injury-induced plasticity of the vlOFC circuitry leads to an overall reduction of vlOFC output.…”

“…Here we show that direct chemo-and optogenetic activation of glutamatergic neurons in the vlOFC relieves hypersensitivity associated with peripheral neuropathy in mice, as does boosting of glutamatergic inputs from the VM. The idea that augmenting excitation of the vlOFC is analgesic is supported by previous reports that pharmacological administration of glutamate in the vlOFC reduces tail-flick reflex responses (Zhang et al, 1997) and that activation of pyramidal neurons in the anterior vlOFC attenuates trigeminal pain (Sheng et al, 2020). Although boosting glutamatergic output from the vlOFC to the vlPAG reversed mechanical hypersensitivity in SNI mice, inhibiting the activity of these neurons (either directly or by inhibiting VM inputs) did not exacerbate these pain responses.…”

“…Glutamatergic neuron activity was not altered in SNI mice compared with sham mice in the three OFC subregions (8.949% versus 5.018%) (Figures S2E and S2F), but given this low level of activity, putative SNI-induced reductions may be difficult to resolve. A reduction in pyramidal cell activity was seen in the vlOFC after chronic constriction of the infraorbital nerve (Sheng et al, 2020). We then recorded intrinsic activities of pyramidal neurons and GABAergic neurons ex vivo in vlOFC layer 5 in acute brain slices from both SNI and sham mice.…”

Unilateral facial injection of Botulinum neurotoxin A attenuates bilateral trigeminal neuropathic pain and anxiety-like behaviors through inhibition of TLR2-mediated neuroinflammation in mice

“…Our previous study demonstrated that BoNT/A injection attenuates depression-like behavior induced by chronic stress in mice, possible via upregulation of the expression of BDNF in the hippocampus [ 8 ]. Depression and anxiety are often observed in patients with chronic pain, with a prevalence of 30% to 50% [ 9 ]. Recent studies have shown that neuropathic pain causes anxiety and depression-like behaviour in mice [ 9 ].…”

“…Depression and anxiety are often observed in patients with chronic pain, with a prevalence of 30% to 50% [ 9 ]. Recent studies have shown that neuropathic pain causes anxiety and depression-like behaviour in mice [ 9 ]. However, the mechanisms underlying analgesic, anti-depressant or anxiolytic of BoNT/A therapy is still largely unclear.…”