Characterization of incisional and inflammatory pain in rats using functional tools of MRI

Abstract

Underlying mechanisms of hyperalgesia differ with regard to the pain entities, which are well-modeled in animals for systematic studies. However, neuroimaging in different animal pain models often lacks clinical relevance and consistency with behavioral studies, which hinders the translation of results. Whereas mechanical stimulation is commonly used to explore hyperalgesia in animals and humans, functional magnetic resonance imaging (fMRI) studies frequently use electrical or heat stimuli to evaluate brain responses relevant to pain and hyperalgesia. To characterize the magnetic resonance (MR) representations of mechanical hyperalgesia after incision and inflammation, we aimed to investigate whole brain functional activities during innocuous and noxious mechanical or electrical stimulation (IMS/NMS; IES/NES), as well as metabolite levels in the thalamus of rats at rest and during electrical stimulation. In behavioral experiments, animal models of pain showed significant mechanical hyperalgesia, with a peak 24h after both injuries, but lasting longer after inflammation. In imaging experiments, mechanical and electrical stimulation revealed a biphasic BOLD response upon noxious stimulation in pain models. Analyses of the BOLD signal changes revealed significantly higher activation in pain models compared to sham animals. Furthermore, significant differences were present upon NMS (but not NES) between incision and inflammation models in all the studied regions except for contralateral somatosensory cortex (S1) and cerebellum (Cb) (F's>4.14, p's<0.05). Additionally, MS (but not ES) induced unexpected bilateral activation of S1 in all three animal groups. Finally, MR spectroscopy (MRS) in the thalamus showed higher concentrations of gamma-aminobutyric acid in both pain models at rest and during stimulation. We conclude that employment of MS in fMRI studies could provide an informative correlate of mechanical hyperalgesia in inflammatory and incisional pain models and might be used to further assess mechanisms and treatments relevant for these clinical pain states.

Keywords: (1)H MRS; BOLD fMRI; GABA; Hyperalgesia; Mechanical stimulation; Postoperative pain model.