Background & Aims
A recent randomized controlled trial of 10 kHz spinal cord stimulation (SCS) in patients with painful diabetic neuropathy (PDN) has demonstrated significant and durable improvements in neurologic status, particularly sensory restoration of the foot (Petersen et al 2023, Argoff et al 2023). In order to gain further mechanistic insight into the improvements in sensory processing by 10kHz SCS, we analyzed responses of primary somatosensory cortex (S1) neurons to vibro-tactile stimuli of the paw in a PDN rat model.
Methods
To develop a model of PDN, rats were given a single effective intraperitoneal dose (60 mg/kg) of streptozotocin (STZ). Two weeks post-injection, we confirmed PDN symptoms and hyperglycemic condition by increased painful response to von Frey (VF) paw probing and elevated blood glucose. Rats were then anesthetized and positioned in a custom stereotactic frame, allowing concurrent craniotomy for recording S1 cortex neurons and laminectomy for lumbar epidural dorsal SCS. First, receptive fields were defined by the firing of cortical neurons to non-nociceptive mechanical stimuli (brush and VF) on the left hind paw. Next, vibrotactile stimulation was applied for 20 seconds onto the RF center with various frequencies (1, 10, and 50Hz) before and during 10 kHz SCS at 30% of motor twitch threshold. Power spectral density (PSD) analysis was used to determine the mechano-sensitivity of S1 cortex (N=4 rats, n=19 neurons).
Results
In comparison to prior experiments on naïve rats, the PSD distribution of cortical neuron firing at each vibration frequency was generally reduced in the PDN rats. However, during the 1Hz vibration, the PSD @ 1 Hz was increased >2x in the presence of 10 kHz SCS, to 3.4E-5 ? 1.0E-5 with 10 kHz SCS from 1.5E-5 ? 4.5E-6 without SCS. Similar increases of the PSD during 10 kHz SCS were seen at 10 Hz vibration (with 10 kHz SCS: 4.2E-4 ? 1.9E-4, vs. without SCS: 1.1E-4 ? 2.7E-5 ) and 50 Hz vibration (with 10 kHz SCS: 2.3E-5 ? 5.5E-6, vs without SCS: 1.1E-5 ? 2.0E-6).
Conclusions
These data suggest that 10 kHz SCS improves the mechanosensitivity of S1 cortex to innocuous afferent signals in PDN rats. In diabetes, where peripheral sensory compromise from chronic hyperglycemia can lead to loss of protective sensation, such ‘tuned amplification’ as provided by 10 kHz SCS in the central nervous system may compensate for the reduced functionality seen in the peripheral sensory systems.
References
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