Chronic electrical stimulation reduces hyperalgesia and associated spinal changes induced by peripheral nerve injury

Abstract

Objectives We aimed to investigate if different protocols of electrical stimulation following nerve injury might improve neuropathic pain outcomes and modify associated plastic changes at the spinal cord level. Materials and Methods Adult rats were subjected to sciatic nerve transection and repair, and distributed in four groups: untreated (SNTR, n = 12), repeated acute electrical stimulation (rAES, 50 Hz, one hour, n = 12), chronic electrical stimulation (CES, 50 Hz, one hour, n = 12), and increasing‐frequency chronic electrical stimulation (iCES, one hour, n = 12) delivered during two weeks following the lesion. The threshold of nociceptive withdrawal to mechanical stimuli was evaluated by means of a Von Frey algesimeter during three weeks postlesion. Spinal cord samples were processed by immunohistochemistry for labeling glial cells, adrenergic receptors, K+‐Cl− cotransporter 2 (KCC2) and GABA. Results Acute electrical stimulation (50 Hz, one hour) delivered at 3, 7, and 14 days induced an immediate increase of mechanical pain threshold that disappeared after a few days. Chronic electrical stimulation given daily reduced mechanical hyperalgesia until the end of follow‐up, being more sustained with the iCES than with constant 50 Hz stimulation (CES). Chronic stimulation protocols restored the expression of β2 adrenergic receptor and of KCC2 in the dorsal horn, which were significantly reduced by nerve injury. These treatments decreased also the activation of microglia and astrocytes in the dorsal horn. Conclusion Daily electrical stimulation, especially if frequency‐patterned, was effective in ameliorating hyperalgesia after nerve injury, and partially preventing the proinflammatory and hyperalgesic changes in the dorsal horn associated to neuropathic pain.

LIFU Alleviates Neuropathic Pain by Improving the KCC2 Expression and Inhibiting the CaMKIV–KCC2 Pathway in the L4–L5 Section of the Spinal Cord

“…All results suggest that downregulation of KCC 2 after PNI plays an essential role in the development of NP [17]. Many studies have found that increasing the expression of KCC 2 significantly relieves NP behavior [9,[18][19][20]. Therefore, learning how to increase the expression of KCC 2 following PNI has great potential value for treating NP.…”

Therapeutic effects of peripherally administrated neural crest stem cells on pain and spinal cord changes after sciatic nerve transection

“…Mechanical withdrawal threshold (MWT) was determined by the same experimenter at 12 weeks after SNT induction using the BEM-404 mechanical analgesia tester [Chinese Academy of Medical Sciences (CAMS), Beijing, China] [21]-the cutoff force was set at 50 g. A rigid tip was applied perpendicularly to the medialplantar surface of the hind paw [29]. Brisk withdrawal or paw flinching was considered a positive response.…”

Potentiation of spinal GABA inhibition as a therapeutic target for chronic neuropathic pain: from transplantation to physical exercise

“…In animals that respond to SCS, a significant increase of GAD 65 was observed in superficial dorsal horn, probably reflecting an increased GABA production following SCS. Recently, López-Álvarez et al (11) used a rat model of sciatic nerve transection and repair to show that chronic stimulation protocols restored the amount of KCC2, which had been significantly decreased by nerve injury, in the dorsal horn of these rats.…”