Described herein are systems and methods for applying extremely low duty-cycle stimulation sufficient to treat chronic inflammation with progressively longer delays (off periods) from an initial stimulation. In particular, described herein are supra-threshold pulses of electrical stimulation sufficient to result in a long-lasting (e.g., >；48 hours) inhibition of pro-inflammatory cytokines and/or effects of chronic inflammation； the delay between initial doses (which may be single-pulse doses) may be extended for subsequent doses, potentially dramatically enhancing battery and device longevity.
