Spinal cord stimulation uses pulsed electrical energy near the spinal cord to manage pain. Initially, this technique applied pulsed energy in the intrathecal space. Presently, neuromodulation involves the implantation of leads in the epidural space. A similar principle utilizes the central nervous system and the peripheral nervous system stimulation in deep/cortical brain stimulation and peripheral nerve stimulation, respectively. Neurostimulation modalities arose as a response to treating the gate control theory of pain by Melzack and Wall. In summary, they posed that pain impulses provoked in the periphery, which are carried by C fibers and A-delta fibers, could be interrupted by stimulating larger A-beta fibers. This interruption is facilitated by the common nerve synapse location in the substantia gelatinosa of the dorsal horn. In other words, stimulation of the touch and vibration nerves “closes the gate” on ascending pain impulses that carry noxious pain stimuli cephalad. Multiple pain systems are responsible for the sensation of pain; these systems are composed of integrative neuronal sets (conduct excitatory or inhibitory signals on the nociceptors). The interrelation between these three systems is responsible for the perceived sensation of pain and the responses associated with it. First, nociceptors receive signals of noxious temperature, chemical, or mechanical stimuli (peripheral neurons). They send this information to second-order neurons located in the spinal cord, mainly in the dorsal horn (central pathways), which are then transmitted via projection neurons to the brainstem (integrative neurons).

Nociceptive Fibers (peripheral pain receptors)

1. Unmyelinated C fibers and lightly myelinated A-beta fibers (small nociceptive fibers, which conduct pain)

2. Myelinated A-beta fibers (large non-nociceptive fibers, which conduct touch, pressure, and vibration)

3. Central pathways (relay neuronal signals to higher brain structures)

1. The primary integrative site in the brain is the thalamus, but other structures also participate in response to pain. Once the brain receives the pain signals, several reactions are generated almost immediately to modify and respond to these signals. These reactions include, but are not limited to, somatic and autonomic reflexes, negative or positive feedback to increase or reduce the pain, endocrine and emotional responses, cortical awareness, or the pain, as well as the memory of the event.

2. The gate control theory of pain, mentioned above, is directly associated with these pain systems. It establishes that C fibers, A-delta fibers (nociceptive), and A-beta fibers (non-nociceptive) can all carry information from the injury site to two different cell types in the dorsal horn of the spinal cord, transmission cells, and inhibitory neurons. Both the nociceptive and non-nociceptive fibers can activate the transmission cells, opening the gate of signals sent to the brain. However, only the non-nociceptive fibers can activate the inhibitory cells, therefore closing the gate.

3. Even though the gate control theory was the initial guiding mechanism of action, modern research has demonstrated that the underlying mechanisms are not clearly understood. There is evidence suggesting that dorsal column stimulation applies a different analgesia mechanism when utilized for neuropathic pain versus ischemic pain. In neuropathic pain, evidence suggests that by altering local neurochemistry, stimulation suppresses hyperexcitability of the wide dynamic range neurons by increasing GABA and serotonin release, which suppresses levels of the excitatory cytokines glutamate and aspartate. On the other hand, the current belief is that ischemic pain alleviation occurs by altering sympathetic tone, achieved by restoring a favorable oxygen supply and demand balance.