Predominant synaptic potentiation and activation in the right central amygdala are independent of bilateral parabrachial activation in the hemilateral trigeminal inflammatory pain model of rats

Abstract

Nociceptive signals originating in the periphery are conveyed to the brain through specific afferent and ascending pathways. The spino-(trigemino-)parabrachio-amygdaloid pathway is one of the principal pathways mediating signals from nociception-specific ascending neurons to the central amygdala, a limbic structure involved in aversive signal-associated emotional responses, including the emotional aspects of pain. Recent studies suggest that the right and left central amygdala play distinct roles in the regulation of nociceptive responses. Using a latent formalin inflammatory pain model of the rat, we analyzed the right–left differences in synaptic potentiation at the synapses formed between the fibers from the lateral parabrachial nucleus and central amygdala neurons as well as those in the c-Fos expression in the lateral parabrachial nucleus, central amygdala, and the basolateral/lateral amygdala after formalin injection to either the right or left side of the rat upper lip. Although the single-sided formalin injection caused a significant bilateral increase in c-Fos-expressing neurons in the lateral parabrachial nucleus with slight projection-side dependence, the increase in the amplitude of postsynaptic excitatory currents and the number of c-Fos-expressing neurons in the central amygdala occurred predominantly on the right side regardless of the side of the inflammation. Although there was no significant correlation in the number of c-Fos-expressing neurons between the lateral parabrachial nucleus and central amygdala in the formalin-injected animals, these numbers were significantly correlated between the basolateral amygdala and central amygdala. It is thus concluded that the lateral parabrachial nucleus-central amygdala synaptic potentiation reported in various pain models is not a simple Hebbian plasticity in which raised inputs from the lateral parabrachial nucleus cause lateral parabrachial nucleus-central amygdala potentiation but rather an integrative and adaptive response involving specific mechanisms in the right central amygdala.

Mild traumatic brain injury is associated with effect of inflammation on structural changes of default mode network in those developing chronic pain

“…Multiple pain disorders have altered grey matter volume (GMV) within the pain matrix [ 12 , 13 ]. Notably, peripheral inflammatory cytokines/chemokines can interact with multiple central pathways as a principal channel for inflammation-brain communication in the development of pain states [ 14 , 15 ]. Considering the potential effect of trauma-induced systemic inflammation on brain cell reaction [ 16 , 17 ], we hypothesized that the inflammatory cytokines level might lead to changes in pain perception via inflammation-brain mechanism [ 18 , 19 ], specifically by affecting cortical morphology alternations in pain-related cognitive modulation following mTBI [ 20 ].…”

Primary Role of the Amygdala in Spontaneous Inflammatory Pain- Associated Activation of Pain Networks – A Chemogenetic Manganese-Enhanced MRI Approach

“…In human patients and animal models of chronic pain, the interconnection between distinct concurrently activated brain areas plays essential roles (Baliki et al, 2014), which provide the basis for the network theory of chronic pain state establishment. Formalin injection results in a selective increase in pERK and c-Fos expression as well as synaptic potentiation in the right CeA, which is accompanied by ectopic sensitization in the non-inflamed hind paw at 3–6 h post-formalin (Carrasquillo and Gereau, 2007; Shinohara et al, 2017; Miyazawa et al, 2018). In addition, pharmacological inhibition of the ERK signaling cascade in the right CeA following intraplantar formalin injection suppresses this bilateral sensitization (Carrasquillo and Gereau, 2007).…”

“…At 17 h (group 1; 6 mice from MnCl 2 -treated and 6 mice from saline-treated) or 21 h (group 2; 6 from MnCl 2 - and 6 from saline-treated mice), 5% formalin was injected into the intraplantar surface of the left hind paw using a microsyringe with a 30-gauge needle (MnCl 2 - and 6 saline-injected mice for each of groups 1 and 2). The evaluation of nocifensive behaviors was done according to methods described previously (Shinohara et al, 2017; Miyazawa et al, 2018). Briefly, each mouse was put immediately to the observation chamber (17 cm × 17 cm × 35 cm transparent acryl frame) and the recording of spontaneous nocifensive behaviors were then started with a web camera (HD Webcam C525; Logicool, Tokyo, Japan).…”

Mild Traumatic Brain Injury is Associated With Effect of Inflammation on Structural Changes of Default Mode Network in Those Developing Chronic Pain 

“…Notably, peripheral in ammatory cytokines/chemokines can interact with multiple central pathways as a principal channel for in ammation-brain communication in the development of pain states (14,15). Considering the potential effect of trauma-induced systemic in ammation on brain cell reaction (16,17), we hypothesized that the in ammatory cytokines level might lead to changes in pain perception via in ammation-brain mechanism (18,19), speci cally by affecting cortical morphology alternations in pain-related cognitive modulation following mTBI (20).…”