Spinal neurovascular coupling is preserved despite time-dependent alterations of spinal cord blood flow responses in a rat model of chronic back pain: implications for functional spinal cord imaging.

Abstract

Functional magnetic resonance imaging has been used to investigate nociceptive processes in patients with chronic pain. However, the results may be confounded with changes in neurovascular coupling induced by chronic pain. The objective of this study was to examine spinal neurovascular coupling in a rat model of chronic back pain induced by muscle inflammation. Rats received 150 µL intramuscular injections of either complete Freund adjuvant (CFA: n = 18) or saline (control [CTL]: n = 18) in L5-L6 paravertebral muscles. Under 1.2% isoflurane anesthesia, spinal cord blood flow (SCBF) and local field potentials evoked by electrical stimulation of the sciatic nerve were recorded simultaneously in the lumbar enlargement of the spinal cord, 14 or 28 days after the injections. Mechanical hypersensitivity was observed in CFA rats compared with CTL rats for the back ( P < 0.001) and hind paws ( P < 0.01). Spinal cord blood flow response amplitude and local field potential amplitude were not significantly different between groups (day 14: P > 0.5; day 28: P > 0.6). However, the time course of SCBF responses was different between groups on day 14 ( P < 0.001) and day 28 ( P < 0.001). Nevertheless, neurovascular coupling was comparable between groups on days 14 and 28, whether neurovascular coupling was calculated with the amplitude or the area under the curve of SCBF responses (all P > 0.2). These results indicate that spinal hemodynamic changes reflect neuronal activity in this animal model, although the time course of SCBF responses is affected by chronic inflammatory back pain. This warrants a careful use of spinal functional magnetic resonance imaging in animal models and patients with chronic back pain.