The role of the dorsolateral funiculi in the pain relieving effect of spinal cord stimulation: a study in a rat model of neuropathic pain
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Activation of the dorsal columns is relayed to supraspinal centers, involved in pain modulation, probably via the descending fibers in the dorsolateral funiculi (DLF). The present study examines the role of the DLF in the attenuation of pain-related signs by spinal cord stimulation (SCS). Several groups of rats were subjected to nerve injury and to chronic bilateral DLF lesions at C5–7 level. In each animal, two sets of miniature electrodes were implanted, a caudal system placed in the dorsal epidural space at low thoracic level and another implanted over the dorsal column nuclei, rostral to the lesions. Stimulation (50 Hz, 0.2 ms; 70 % of motor threshold) was applied for 5 min via either of the electrodes. Behavioral tests were used to assess the effects of SCS on the nerve injury-induced mechanical and cold hypersensitivity and heat hyperalgesia. Prior to application of SCS, antagonists to either of GABAA or B, 5-HT1 or 1–2 or α/β-adrenergic receptors were injected i.p. Both stimulations produced comparable decreases (80–90 % of the control) of neuropathic manifestations in rats with intact spinal cords. DLF lesions attenuated the effects of both types of stimulation by about 50 %. Pretreatment with receptor antagonists differentially counteracted the effects of rostral and caudal stimulation; the inhibition with rostral stimulation generally being more prominently influenced. These results provide further support to the notion of important involvement of brainstem pain modulating centers in the effects of SCS. A major component of the inhibitory spinal–supraspinal–spinal loop is mediated by fibers running in the DLF.
KeywordsSpinal cord stimulation Neuropathic pain Dorsolateral funiculus GABA 5-HT Pain modulation
Spinal cord stimulation
Dorsal column nuclei stimulation
Spared nerve injury
Paw withdrawal duration
Paw withdrawal latency
Rostral ventromedial medulla
The authors thank Sawsan Sharrouf and Bassem Najm for their technical assistance. This work was supported by a grant from the Swedish Research Council. Formal approval to conduct the experiments described has been obtained from the Animal Care Facility at the American University of Beirut and could be provided upon request. All efforts were made to minimize the number of animals used and their suffering.
Conflict of interest
There are no conflicts of interests.
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