Characterization of a new animal model for evaluation of persistent postthoracotomy pain

• Published in: Anesthesia and analgesia Vol. 99; no. 5; pp. 1453 - 1460
• Main Authors: BUVANENDRAN, Asokumar, KROIN, Jeffrey S, KERNS, James M, NAGALLA, Subhash N. K, TUMAN, Kenneth J
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott 01.11.2004
• Subjects: Analgesics - therapeutic use; Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Chronic Disease; Cold Temperature; Disease Models, Animal; Dose-Response Relationship, Drug; Male; Medical sciences; Pain Measurement; Pain, Postoperative - drug therapy; Pain, Postoperative - pathology; Pain, Postoperative - physiopathology; Peripheral Nerves - pathology; Physical Stimulation; Rats; Rats, Sprague-Dawley; Ribs - pathology; Ribs - surgery; Thoracotomy; Tissue Fixation; Weight Gain - physiology; Animal model; Anesthesia; Pain
• ISSN: 0003-2999; 1526-7598
• DOI: 10.1213/01.ANE.0000134806.61887.0D

Chronic pain after thoracotomy is common, although its basis and therapy have not been well characterized. In this study we characterize the allodynic responses (mechanical and cold) as well as the histopathologic changes after thoracotomy and rib retraction in rats. The antinociceptive effect of systemic and intrathecal analgesics was also evaluated. Male Sprague-Dawley rats were anesthetized and the right 4th and 5th ribs surgically exposed. The pleura was opened between the ribs and a retractor placed under both ribs and opened 8 mm. Retraction was maintained for 5, 30, or 60 min. Control animals had pleural incision only. Beginning Day 2 postsurgery, animals were tested for mechanical allodynia using calibrated von Frey filaments and cold allodynia using acetone applied to the incision site. Two weeks after surgery, animals were tested for reduction of allodynia with intraperitoneal and intrathecal injections of analgesics. Intercostal nerve histology was examined at 14 days postsurgery. Allodynia developed in 50% of the animals with 60 min retraction but in only 11% and 10% of animals when the retraction time was 5 and 30 min, respectively, and in none of the control animals. Allodynic animals showed extensive axon loss in the intercostal nerves of the retracted ribs. Allodynia appeared by Day 10 in the rib-retraction model and lasted at least 40 days. Systemic morphine sulfate (50% effective dose [ED(50)], 1.06 mg/kg) and gabapentin (ED(50), 24.2 mg/kg), as well as intrathecal morphine (ED(50), 1.19 nmol), gabapentin (ED(50), 13.8 nmol), clonidine (ED(50), 72.7 nmol), and neostigmine (ED(50), 0.54 nmol) reduced allodynia. Rib-retraction in rats for 60 min produces allodynia that lasts more than 1 mo, and this allodynia is reduced by morphine, gabapentin, clonidine, and neostigmine. This new model may be useful for quantifying the efficacy of techniques to reduce the frequency and severity of long-term postthoracotomy pain.