Impaired muscarinic modulation of the rat prelimbic cortex in neuropathic pain is sexually dimorphic and associated with cold allodynia

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Cholinergic modulation of the brain cortex is critical for cognitive processes, and altered cholinergic modulation of the prefrontal cortex is emerging as an important mechanism of neuropathic pain. Sex differences in pain prevalence and perception are well known, yet the precise nature of the mechanisms responsible for sexual dimorphism in chronic neuropathic pain are poorly understood. Here we investigated potential sex differences in cholinergic modulation of layer five commissural pyramidal neurons of the rat prelimbic cortex in control conditions and in the SNI model of neuropathic pain. We discovered that cholinergic modulation is stronger in cells from male compared with female rats, and that in neuropathic pain rats, cholinergic excitation of pyramidal neurons was more severely impaired in males than in females. Finally, we found that selective pharmacological blockade of the muscarinic M1 subunit in the prefrontal cortex induces cold sensitivity (but not mechanical allodynia) in naïve animals of both sexes.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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