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A 1994 meta-analysis showed that higher doses of nicotine gum (4mg) are more effective for heavy smokers than lower doses (2mg)

In addition to direct neuronal activation, MC-derived mediators further contribute to neuronal sensitization by increasing the activity of membrane-bound TRP channels, particularly TRPA1 and TRPV1, which lower the activation threshold of neurons and establish a state of peripheral hyperexcitability (40, 91, 103)