Alterations in brain neurocircuitry following treatment with the chemotherapeutic agent paclitaxel in rats

Abstract

Highlights Imaging the reorganization of pain neural circuitry within 8 days of chemotherapy. Using rat model of neuropathy with multimodal MRI. Showing loss of anticorrelation between prefrontal cortex and PAG. Identifying the interaction between periaqueductal gray and brainstem raphe.

Serotoninergic pain modulation from the rostral ventromedial medulla (RVM) in chemotherapy‐induced neuropathy: The role of spinal 5‐HT3 receptors

“…By showing, for the first time, that the activity of serotoninergic RVM neurons is increased in a CIN model, the present study indicates an increased recruitment of descending 5‐HT‐mediated pain modulation during CIN. Based on a recent preliminary imaging study in a short‐term model of paclitaxel‐induced CIN which pointed to dysregulation of the PAG–RVM circuit (Ferris et al, ), it will be important to study the RVM along with the PAG in our paclitaxel‐induced long‐term model of CIN. This will allow to evaluate whether the PAG–RVM circuit is important for initiation or for maintenance of chronic pain.…”

“…In paclitaxel‐induced CIN, there are increases of spontaneous and evoked firing of neurons in the periaqueductal grey matter (PAG), a key area involved in descending pain modulation (Samineni, Premkumar, & Faingold, ). Furthermore, in a recent exploratory study using diffusion‐weighted magnetic resonance in a short‐duration model of paclitaxel‐induced CIN, alterations in the activity of higher brain centres targeting the PAG were reported (Ferris et al, ). The dysregulation of central components of the somatosensory system during CIN is probably due to the aforementioned peripheral effects of paclitaxel (Cavaletti & Marmiroli, ) since the drug is poorly transported across the blood–brain barrier (Cavaletti et al, ).…”

Positive Allosteric Modulation of CB1 Cannabinoid Receptor Signaling Enhances Morphine Antinociception and Attenuates Morphine Tolerance Without Enhancing Morphine- Induced Dependence or Reward

“…Mechanisms underlying the development of paclitaxelinduced neuropathic allodynia remain incompletely understood. Loss of intraepidermal nerve fibers, abnormal mitochondrial function, infiltration of damage-associated molecular patterns and pro-inflammatory cytokine and chemokines within dorsal root ganglia and spinal cord as well as aberrant brain resting state connectivity have all been implicated in contributing to chemotherapy-induced neuropathy produced by paclitaxel (Ferris et al, 2019;Staff et al, 2020).…”

Role of Spinal Cord α2-Adrenoreceptors in Noradrenergic Inhibition of Nociceptive Transmission During Chemotherapy-Induced Peripheral Neuropathy

“…At the supraspinal level, the periaqueductal gray matter (PAG), a key area of the descending pain modulatory system, shows increases in spontaneous and evoked neuronal firing (Samineni et al, 2017). Furthermore, in a recent exploratory study using diffusion weighted magnetic resonance, alterations in the activity of the PAG were reported (Ferris et al, 2019). Using an animal model of paclitaxel-induced CIPN, we recently reported increases in the activity of serotoninergic neurons of the rostroventromedial medulla (RVM), an area that relays descending modulation from the PAG to the spinal cord (Costa-Pereira et al, 2019).…”