Stimulation of the Central and Peripheral Nervous System for the Control of Pain

After suffering some setbacks since its introduction in 1967, stimulation of the spinal and peripheral nervous systems has undergone rapid development in the last ten years. Based on principles enunciated in the Gate Control Hypothesis that was published in 1968, stimulation-produced analgesia [SPA] has been subjected to intensive laboratory and clinical investigation. Historically, most new clinical ideas in medicine have tended to follow a three-tiered course. Initial enthusiasm gives way to a reappraisal of the treatment or modality as side-effects or unanticipated problems arise. The last and third phase proceeds at a more measured pace as the treatment is refined by experience. This review is divided into three parts as it traces the progress of spinal cord stimulation [SCS] and peripheral nerve stimulation [PNS]. The review commences with a discussion of the theory of SCS and PNS, and is followed by early reports during which it became apparent that the modality is essentially only effective in the treatment of neuropathic pain. The last section describes the modern experience including efficacy in specific types of pain and concludes with recent accomplishments that dramatize the relief of pain which can be achieved in nonoperable peripheral vascular disease or myocardial ischemia. Over the years, a search for those transmitters that might be influenced by spinal cord stimulation focused on somatostatin, cholecystokinin (CCK), vasoactive intestinal polypeptide (VIP), neurotensin and other amines, although only substance "P" was implicated. More recently, in animal studies, evidence that GABA-ergic systems are affected may explain the frequent successful suppression of allodynia that follows spinal cord stimulation. During the past eight years, much attention has been directed to studies that use a chronic neuropathic pain model. While PNS held significant promise as a pain relieving modality, early electrode systems and their surgical implantation yielded variable results due to evolving technical and surgical skills. These results dramatically reduced the continued development of PNS, which then gave way to a preoccupation with SCS. Modern development of SCS with outcome studies, particularly in relation to failed back surgery syndrome [FBSS] and the outcome of peripheral nerve surgery for chronic regional pain syndromes, has earned both modalities a place in the ongoing management of patients with intractable neuropathic pain. The last section, dealing with pain of peripheral vascular and myocardial ischemia, is perhaps one of the more exciting developments in stimulation produced analgesia and as the papers discussed demonstrate, can provide a level of analgesia and efficacy that is unattainable by other treatment modalities. SCS and PNS has an important role to play in the management of conditions that are otherwise refractory to conservative or other conventional management. Stimulation-produced analgesia (SPA) is centuries old (Mayer and Liebeskind, 1974; Long, 1975). Natural sources of electricity, such as the electric eel and other fishes, have been used for the treatment of pain. In China, electric current applied to acupuncture needles has been in use for centuries and medical literature during the 19th century is filled with scientific and lay application of electrical stimulators promoted for treating pain (MacKay, 1841)(Long, 1986; Chapman, 1990). All but a few reports curiously ignored any association between the nervous system and the mystical properties that electricity held for the treatment of numerous human ailments. Although in 1959 Althaus (1959, 1970) reported that both analgesia and anesthesia occurred in the presence of paresthesia during electrical stimulation of major nerve trunks, he did not significantly influence current medical thinking. Although an interest in neuromodulation truly began with the publication of Gate Theory by Melzack and Wall(Melzack and Wall, 1965; Wall and Sweet, 1967; Shealey et al., 1970; Sweet and Wepsic, 1974; Long and Hagfors, 1975). It was the fortuitous association between Wall, Sweet, and Sweet's resident Shealey that set in motion any actual progress (Sweet and Wepsic, 1974; Shealey, 1975) and research and development that has resulted in the the present status of spinal cord and nervous system stimulation for the control of pain (Wall, 1973; Pineda, 1975). Indeed, only 2 years later Shealey described the use of dorsal column stimulation (DCS), now known as spinal cord stimulation (SCS) for the control of chronic pain (Shealey et al., 1970). Because SCS failed to relieve many patients of their pain, interest in the use of peripheral nerve stimulation increased (Sweet and Wepsic, 1968; Picaza et al., 1975; Nashold et al., 1979). Indeed, it was the failure to control pain in many patients that stimulated clinicians to seek improved methods to screen their patients beforehand. While using a transcutaneous stimulation device, Shealey noted that some patients obtained control of their pain, obviating the need to implant a stimulator. Long and Hagfors (1975), who had designed and tested a stimulator, used a square-wave pulse with controllable amplitude and frequency and presented their data at the inaugural meeting of what subsequently became the International Society for the Study of Pain, 1973. Although the use of transcutaneous nerve stimulation is another application of SPA, it has been more widely studied for the treatment of acute musculoskeletal syndromes (Long and Carolan, 1975; Sternbach et al., 1976; Procacci et al., 1977; Andersson, 1979; Ali et al., 1981; Morritz, 1982). Its use for specific peripheral nerve stimulation (PNS) is a separate topic and beyond the scope of this paper. With regard to the mechanism of SPA and its introduction as a term in neurophysiology, the seminal paper is that of Mayer and Liebeskind (1974). It was Reynolds (1969), however, who demonstrated that focal stimulation of the lateral margin of the periaqueductal gray (PAG) prevented nociceptive responses in rats during abdominal surgery; later, Basbaum and Fields(1978; Willis, 1985) proposed a model describing descending pathways that modulate pain transmission. The components of this model include neurons in the PAG, the nucleus raphe magnus (NRM) forming the pathway from midbrain to the dorsal horn of the spinal cord, the role of which is to inhibit nociceptors by activating the inhibitory interneurons and prevent ascension of nociception. This inhibition may be both pre and postsynaptic. Projections from the locus ceruleus (LC) and the parabrachial complex (PB) and the magnocellular part of the nucleus reticularis gigantocellularis (Rmc) are also involved. This system can influence the spinothalamic tract (STT), the main pathway for pain transmission in humans (Willis, 1985). Fields and Basbaum demonstrated that the neuropeptide transmitter substance P is affected by this descending influence which, participating in the "Gate mechanism" normally modulates pain transmission at the level of the dorsal horn (Basbaum and Fields, 1978). To carry this analogy further, suppression of chronic pain from various parts of the body explains why stimulation of the dorsal columns (DC) of the spinal cord has been a particular target (Dimitrijevic et al., 1980; Barolat et al., 1991). Primary cutaneous afferents corresponding to all parts of the body below the level of the stimulating electrode, and large fibers in particular, are considered to be selectively activated because of their low stimulation threshold. Stimulation of these fibers provides a tingling sensation(paresthesia) in the corresponding dermatome, thus enabling the physician to direct these paresthesias to the painful area by SCS (Law and Miller, 1982; Struijk et al., 1993b).