Nocifensive behavior-related laser heat-evoked component in the rostral agranular insular cortex revealed using morphine analgesia

Wu, Wen-Yi; Liu, Chan-Ying; Tsai, Meng‐Li; Yen, Chen‐Tung

doi:10.1016/j.physbeh.2015.11.020

Cited by 9 publications

(6 citation statements)

References 29 publications

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“…and in a stereotaxic frame. Guide cannulae (28-gauge) were bilaterally implanted into the RAIC (1.0 mm anterior to bregma, ±4.7 mm lateral from the midline, 5.8 mm beneath the surface of the skull; Han et al, 2015; Jung et al, 2016; Wu et al, 2016). Rats were allowed to recover for 1 week after cannula implantation.…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, human fMRI studies document a relationship between the IC and chronic neuropathic pain conditions (Garcia-Larrea and Peyron, 2013; Tseng et al, 2013), and interestingly, rostral regions of the IC are activated during noxious somatosensory stimulation (Coghill et al, 1999; Brooks et al, 2002). The rostral agranular IC (RAIC) in rats is essential for modulating nociception (Wu et al, 2016) and is implicated in pain behavior (Burkey et al, 1996; Jasmin et al, 2003). Recently, Jung et al (2016) found that lesions in RAIC diminished pain-related behaviors in neuropathic pain models.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of Mammalian Target of Rapamycin (mTOR) Signaling in the Insular Cortex Alleviates Neuropathic Pain after Peripheral Nerve Injury

Kwon

Han

Kim

et al. 2017

Front. Mol. Neurosci.

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Injury of peripheral nerves can trigger neuropathic pain, producing allodynia and hyperalgesia via peripheral and central sensitization. Recent studies have focused on the role of the insular cortex (IC) in neuropathic pain. Because the IC is thought to store pain-related memories, translational regulation in this structure may reveal novel targets for controlling chronic pain. Signaling via mammalian target of rapamycin (mTOR), which is known to control mRNA translation and influence synaptic plasticity, has been studied at the spinal level in neuropathic pain, but its role in the IC under these conditions remains elusive. Therefore, this study was conducted to determine the role of mTOR signaling in neuropathic pain and to assess the potential therapeutic effects of rapamycin, an inhibitor of mTORC1, in the IC of rats with neuropathic pain. Mechanical allodynia was assessed in adult male Sprague-Dawley rats after neuropathic surgery and following microinjections of rapamycin into the IC on postoperative days (PODs) 3 and 7. Optical recording was conducted to observe the neural responses of the IC to peripheral stimulation. Rapamycin reduced mechanical allodynia and downregulated the expression of postsynaptic density protein 95 (PSD95), decreased neural excitability in the IC, thereby inhibiting neuropathic pain-induced synaptic plasticity. These findings suggest that mTOR signaling in the IC may be a critical molecular mechanism modulating neuropathic pain.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhibition of Mammalian Target of Rapamycin (mTOR) Signaling in the Insular Cortex Alleviates Neuropathic Pain after Peripheral Nerve Injury

Kwon

Han

Kim

et al. 2017

Front. Mol. Neurosci.

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“…Earlier studies have used CO 2 lasers to produce thermal pain stimuli (Kuo and Yen 2005, Zhang et al 2011, Wu et al 2016). Here, we chose to use a blue laser for the following reasons.…”

Section: Resultsmentioning

confidence: 99%

Deciphering neuronal population codes for acute thermal pain

et al. 2017

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Objective Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. Current pain research mostly focuses on molecular and synaptic changes at the spinal and peripheral levels. However, a complete understanding of pain mechanisms requires the physiological study of the neocortex. Our goal is to apply a neural decoding approach to read out the onset of acute thermal pain signals, which can be used for brain–machine interface. Approach We used micro wire arrays to record ensemble neuronal activities from the primary somatosensory cortex (S1) and anterior cingulate cortex (ACC) in freely behaving rats. We further investigated neural codes for acute thermal pain at both single-cell and population levels. To detect the onset of acute thermal pain signals, we developed a novel latent state-space framework to decipher the sorted or unsorted S1 and ACC ensemble spike activities, which reveal information about the onset of pain signals. Main results The state space analysis allows us to uncover a latent state process that drives the observed ensemble spike activity, and to further detect the ‘neuronal threshold’ for acute thermal pain on a single-trial basis. Our method achieved good detection performance in sensitivity and specificity. In addition, our results suggested that an optimal strategy for detecting the onset of acute thermal pain signals may be based on combined evidence from S1 and ACC population codes. Significance Our study is the first to detect the onset of acute pain signals based on neuronal ensemble spike activity. It is important from a mechanistic viewpoint as it relates to the significance of S1 and ACC activities in the regulation of the acute pain onset.

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“…These data suggest that oxytocin-induced antinociception in RAIC is mediated by a local OTR-GABA A receptor activation and involves the participation of a descending noradrenergic modulatory mechanism probably promoted by LC disinhibition (Jasmin et al, 2003). However, since the BRL 44408 effect was modest, we could infer that other descending mechanisms or corticocortical interactions are also involved (Ohara et al, 2005;Xie et al, 2009;Chen et al, 2010;Jung et al, 2016;Wu et al, 2016). Indeed, it has been shown that PVN electrical stimulation enhances c-fos expression not only in LC but also in the RM and PAG (Condés-Lara et al, 2015), both structures related with descending pain inhibition by serotonergic and opioidergic transmission.…”

Section: Pvn Oxytocinergic Innervations Toward Raicmentioning

confidence: 88%

The Rostral Agranular Insular Cortex, a New Site of Oxytocin to Induce Antinociception

et al. 2020

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The rostral agranular insular cortex (RAIC) is a relevant structure in nociception. Indeed, recruitment of GABAergic activity in RAIC promotes the disinhibition of the locus ceruleus, which in turn inhibits (by noradrenergic action) the peripheral nociceptive input at the spinal cord level. In this regard, at the cortical level, oxytocin can modulate the GABAergic transmission; consequently, an interaction modulating nociception could exist between oxytocin and GABA at RAIC. Here, we tested in male Wistar rats the effect of oxytocin microinjection into RAIC during an inflammatory (by subcutaneous peripheral injection of formalin) nociceptive input. Oxytocin microinjection produces a diminution of (1) flinches induced by formalin and (2) spontaneous firing of spinal wide dynamic range cells. The above antinociceptive effect was abolished by microinjection (at RAIC) of the following: (1) L-368899 (an oxytocin receptor [OTR] antagonist) or by (2) bicuculline (a preferent GABA A receptor blocker), suggesting a GABAergic activation induced by OTR. Since intrathecal injection of an a 2A -adrenoceptor antagonist (BRL 44408) partially reversed the oxytocin effect, a descending noradrenergic antinociception is suggested. Further, injection of L-368899 per se induces a pronociceptive behavioral effect, suggesting a tonic endogenous oxytocin release during inflammatory nociceptive input. Accordingly, we found bilateral projections from the paraventricular nucleus of the hypothalamus (PVN) to RAIC. Some of the PVN-projecting cells are oxytocinergic and destinate GABAergic and OTRexpressing cells inside RAIC. Aside from the direct anatomic link between PVN and RAIC, our findings provide evidence about the role of oxytocinergic mechanisms modulating the pain process at the RAIC level.

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Nocifensive behavior-related laser heat-evoked component in the rostral agranular insular cortex revealed using morphine analgesia

Cited by 9 publications

References 29 publications

Inhibition of Mammalian Target of Rapamycin (mTOR) Signaling in the Insular Cortex Alleviates Neuropathic Pain after Peripheral Nerve Injury

Inhibition of Mammalian Target of Rapamycin (mTOR) Signaling in the Insular Cortex Alleviates Neuropathic Pain after Peripheral Nerve Injury

Deciphering neuronal population codes for acute thermal pain

The Rostral Agranular Insular Cortex, a New Site of Oxytocin to Induce Antinociception

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