Objective To investigate the effects of percutaneous radiofrequency thermocoagulation on pain and serum C-reactive protein (CRP), interleukin-1β (IL-1β), prostaglandin E2 (PGE2), interleukin-10 (IL-10), 5-hydroxytryptamine (5-HT) levels, in order to provide reference for clinical treatment. Methods According to the random number table method, the patients with chronic neck and shoulder pain (50 cases) admitted to Zhanjiang Nanyou Hospital from January 2018 to January 2021 were divided into the control group (25 cases, drug combined with massage and acupuncture) and the observation group (25 cases, percutaneous radiofrequency thermocoagulation), the patients in the control group were treated for 7 days as a course of treatment, with a total of 2 courses of treatment, the patients in the observation group were treated once, and all were followed up for 3 months. The clinical efficacy of the two groups of patients after treatment, overall recurrence rate after 3 months of follow-up were compared, clinical symptom scores, serum CRP, IL-1β, PGE2, IL-10, 5-HT levels before treatment and after 2 weeks of treatment, visual analogue scale (VAS) before treatment and after 1~2 weeks of treatment , and the quality of life scale (SF-36) score before treatment and after 1~3 months treatment were compared between the two groups. Results After treatment, the total clinical effective rate of the observation group was 96.00%, which was significantly higher than 68.00% of the control group; compared with before treatment, the symptom scores of pain, swelling and functional limitation, serum CRP, IL-1β, PGE2, 5-HT levels and VAS scores after 1~2 weeks of treatment in the two groups significantly decreased, and the observation group was significantly lower than the control group, the levels of IL-10 after 2 weeks of treatment and the SF-36 scores at 1 and 3 months after treatment in the two groups significantly increased, and the observation group was significantly higher than the control group (all P<0.05); after follow-up, statistics showed that the total recurrence rate of patients in the observation group was lower than that in the control group, but there was no significant difference between the two groups (P>0.05). Conclusion Percutaneous radiofrequency thermocoagulation can improve the clinical symptoms of patients with chronic neck and shoulderpain, reduce the level of inflammatory factors, relieve neck and shoulder pain, improve the quality of life, and has a significant effect, at the same time, compared with drugs combined with massage and acupuncture, this treatment plan can reduce the recurrence rate of neck and shoulder pain to a certain extent.