Administration of spinal analgesics around the spinal cord requires safety assessment due to the possibility of inflicting neurotoxic damage. Thus, neurotoxicologic evaluation should be performed for effective, safer spinal antinociception. Every potential agent for spinal administration should be studied in animals for its effects on spinal blood flow or vessels before any attempt is made to administer the drug to humans. As the spinal cord normally has a marginal blood flow, excessive vasoconstriction might produce spinal cord ischemia and consequent neurologic dysfunction. This review therefore focuses on the effects on the spinal circulation induced by well-known spinal analgesics employed in the treatment of acute and chronic pain disorders.