NAD+ · research summary

Cannabinoid CB1 Receptor Regulates Spinal Dorsal Horn Synaptic Plasticity in a Mouse Model of Neuropathic Pain through the CB1R/SREBP1/NAMPT/SIRT1 Metabolic Regulatory Framework.

Brain and behavior · 2026. Summary drawn from the study's full text. Each statement is followed by the exact sentence it comes from. This is a research summary, not medical advice.

Study type

Experimental study using a chronic constriction injury mouse model to investigate CB1R modulation effects on pain and metabolism.
“A chronic constriction injury (CCI) mouse model was used.”

Subjects

68 male KM mice, 6 weeks old, weighing 20–25 g.
“A total of 68 male KM mice (6 weeks old, 20–25 g) were used.”

Sample size

68 mice initially, with 64 included in the final electrophysiological analysis.
“After applying predefined quality exclusion criteria, 64 mice were included in the final analysis.”

Duration

Behavioral assessments were conducted up to Day 14 post-surgery, with drug administration from Day 11 to 13.
“Mechanical and thermal hypersensitivity were assessed at baseline, Day 7, and Day 14 post‐surgery.”

Reported findings

CB1R activation reduced mechanical and thermal hypersensitivity and attenuated C-fiber-evoked spinal long-term potentiation.
“CB1R activation alleviated CCI‐induced mechanical and thermal hypersensitivity and attenuated exaggerated C‐fiber–evoked spinal long‐term potentiation, whereas CB1R inhibition produced the opposite tendency.”
CB1R antagonist AM251 reduced spinal protein levels of CB1R, SREBP1, and NAMPT while increasing SIRT1.
“AM251 reduced spinal dorsal horn CB1R, SREBP1, and NAMPT protein levels by 49.0%, 37.8%, and 57.5%, respectively, compared with untreated CCI mice, while increasing SIRT1 protein by 17.8% (p < 0.01).”
CB1R agonist WIN55,212-2 increased spinal protein levels of CB1R, SREBP1, and NAMPT while reducing SIRT1.
“In contrast, WIN55,212‐2 increased CB1R, SREBP1, and NAMPT protein levels by 24.5%, 23.7%, and 17.2%, respectively, and reduced SIRT1 protein by 28.8% compared with untreated CCI mice (p < 0.01).”

Limitations stated by the authors

Findings are based on pharmacological modulation where drugs may have off-target effects, and receptor specificity was not confirmed with genetic models.
“It is well‐documented that AM251 is not an absolutely selective CB1R antagonist/inverse agonist and may exhibit off‐target effects, while WIN55,212‐2 can also activate CB2R at certain concentrations.”

Source: PubMed 42867128 · DOI 10.1002/brb3.71837 · all study summaries

Reported findings

CB1R activation reduced mechanical and thermal hypersensitivity and attenuated C-fiber-evoked spinal long-term potentiation.

“CB1R activation alleviated CCI‐induced mechanical and thermal hypersensitivity and attenuated exaggerated C‐fiber–evoked spinal long‐term potentiation, whereas CB1R inhibition produced the opposite tendency.”

CB1R antagonist AM251 reduced spinal protein levels of CB1R, SREBP1, and NAMPT while increasing SIRT1.

“AM251 reduced spinal dorsal horn CB1R, SREBP1, and NAMPT protein levels by 49.0%, 37.8%, and 57.5%, respectively, compared with untreated CCI mice, while increasing SIRT1 protein by 17.8% (p < 0.01).”

CB1R agonist WIN55,212-2 increased spinal protein levels of CB1R, SREBP1, and NAMPT while reducing SIRT1.

“In contrast, WIN55,212‐2 increased CB1R, SREBP1, and NAMPT protein levels by 24.5%, 23.7%, and 17.2%, respectively, and reduced SIRT1 protein by 28.8% compared with untreated CCI mice (p < 0.01).”

Limitations stated by the authors

Findings are based on pharmacological modulation where drugs may have off-target effects, and receptor specificity was not confirmed with genetic models.

“It is well‐documented that AM251 is not an absolutely selective CB1R antagonist/inverse agonist and may exhibit off‐target effects, while WIN55,212‐2 can also activate CB2R at certain concentrations.”