Radiotelemetric and Symptomatic Evaluation of Pain in the Rat After Laparotomy: Long-Term Benefits of Perioperative Ropivacaine Care. [Charlet et al 2011]
Mechanisms and therapeutics for addressing acute pain from recent surgery are well understood in comparison to those associated with chronic pain.
Charlet and others describe the use of radiotelemetry to monitor physiological parameters in a rat laparotomy model for the purpose of behavioral and hyperalgesia studies. They point out that mean heart rate is often unaffected in pain models, but evidence from human studies suggests that heart rate variability (HRV, measured from the RR interval of electrocardiogram) may provide a useful index for evaluating pain.
For preliminary studies, to characterize the model, Male Sprague-Dawley rats were implanted with CTA-F40 radiotelemetry transmitters to provide ECG, temperature and activity data using Data Exchange Matrices (Data Sciences International). Standardized laparotomy may be used as an acute pain model and is required for implantation of the telemetry device. Prior to surgery, baseline activity measurements were gathered using a non-invasive system (ActiV-meter, Bioseb). Since it was not possible to obtain cardiovascular parameters prior to surgery, data obtained from 15 days post-surgery were used for control purposes, since this was the point in time when they became stabilized. HRV and HR were measured from 20 second ECG segments. For HRV, a domain analysis of RR intervals was used to derive SD1 from the Poincaré plot of RR interval which describes short term HRV by describing successive changes in RR interval. It was possible to describe a global SD1 for each animal. In addition pNN18 was estimated based on an arbitrary threshold change in RR interval of 18ms. Prior to surgery, animals were habituated to handling and testing with von Frey hairs of varying stiffness and therefore force.
Following telemetry device implantation (at laparotomy of standardized technique and duration), animals were studied by telemetry to provide activity, cardiovascular parameters and core temperature. Analgesimetry was performed by an observer blinded to treatment groups, using von Frey hairs applied to the margins of the wound. At day three post-surgery, single doses of established analgesic were infiltrated into the incisional margins (keoprofen, morphine and ropivacaine) under brief inhalational anaesthesia as positive controls.
After surgery, rats showed decreased nocturnal activity and long lasting tachycardia (upto 10 days). Mechanical hyperalgesia was present in animals on von Frey hair testing which was abolished temporarily following topical single dose injection of the analgesic positive controls.
Having characterized a model of hyperalgesia responding to various positive control analgesics, the model was used to evaluate topical infiltration of the wound margins at completion of surgery with the local analgesic ropivacaine or saline. In addition, a distant subcutaneous injection of ropivacaine was given in some animals to control for any systemic effects. In rats receiving topical ropivacaine infiltration, development of hyperalgesia was virtually attenuated for a ten day period. These animals showed reduction in disturbance of circadian rhythm for mobility, heart rate and temperature.
HRV was studied three days postoperatively in the hyperalgesia model before and after ropivacaine infiltration. Mean HR was not significantly influenced by ropivacaine but HRV assessed by SD1, SD(SD1) and pNN18 were significantly different.
Charlet, A; Rodeau, JL; Poisbeau, P. The Journal of Pain. February 2011.