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Mesotherapy, or intradermal therapy, is a therapeutic approach that is gaining popularity, but there is still a significant lack of information on its mechanisms of action or the pharmacokinetics of the therapeutic regimens. This retrospective study on 220 records compared the short-term and long-term effects of mesotherapy using a mixture of drugs versus normal saline solution in the treatment of patients with chronic spinal pain (CSP). At the end of treatment, outcome measures showed a significant improvement (P<0.003) in both groups, which persisted at the follow-up assessments. At 12 weeks of follow-up, the improvement was significantly greater in patients treated with the drug cocktail than with the saline solution (P<0.05). Mesotherapy was effective in patients affected by CSP, with high patient satisfaction reported irrespective of the agent used. Considering the risks and costs of drugs, normal saline solution appears to be the best agent in cost–benefit terms for treating localized pain by mesotherapy in CSP.