Background: One factor affecting spinal cord injury (SCI)-related pain may be nicotine. Case reports have described a worsening of neuropathic pain from smoking and relief from abstinence. Neurobiological correlates also implicate the potential effect of nicotine on SCI-related pain. Method: The current study employed a randomized, placebo-controlled crossover design to examine the effect of nicotine exposure on subtypes of SCI-related pain among smokers and nonsmokers. Results: Whereas nonsmokers with SCI showed a reduction in mixed forms of pain following nicotine exposure, smokers with SCI showed a converse increase in pain with regard to both mixed and neuropathic forms of pain. The exacerbation of pain in chronic nicotine or tobacco users may not only elucidate possible pain mechanisms but may also be of use in smoking cessation counseling among those with SCI. © 2012 Thomas Land Publishers, Inc.