Pain hypersensitivity resulting from peripheral nerve injury depends on
pathological microglial activation in the dorsal horn of the spinal cord. This
microglial activity is critically modulated by P2X7 receptors (P2X7R) and ATP
stimulation of these receptors produces mechanical allodynia, a defining feature
of neuropathic pain. Peripheral nerve injury increases P2X7R expression and
potentiates its cation channel function in spinal microglia. Here, we report a
means to preferentially block the potentiation of P2X7R function by delivering a
membrane permeant small interfering peptide that targets Y382-384, a
putative tyrosine phosphorylation site within the P2X7R intracellular C-terminal
domain. Intrathecal administration of this palmitoylated peptide
(P2X7R379-389) transiently reversed mechanical allodynia caused
by peripheral nerve injury in both male and female rats. Furthermore, targeting
Y382-384 suppressed P2X7R-mediated release of cytokine tumor
necrosis factor alpha and blocked the adoptive transfer of mechanical allodynia
caused by intrathecal injection of P2X7R-stimulated microglia. Thus,
Y382-384 site-specific modulation of P2X7R is an important
microglial mechanism in neuropathic pain.
Homeless individuals are disproportionately likely to experience mental health conditions, and typically face many systemic barriers to access mental health services. This study sought to determine the mental health needs of homeless and recently housed individuals in Canada. A meta‐ethnography was conducted to synthesise existing qualitative data and translate themes across a broader context. Thirty‐five studies on the experiences of 1511 individuals with a history of homelessness were included. Themes were interpreted by comparing and contrasting findings across multiple contexts. Distinct, yet highly interrelated, unmet mental health needs were revealed through personal narratives of trauma, stigmatisation, victimisation, and a lack of basic necessities. Six themes that characterised this population's mental health needs were ontological security, autonomy, hope and purpose, empowerment, social connection and belonging, and access to services. This study revealed homeless individuals' unmet mental health needs to inform social and policy change and improve psychological well‐being.
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