Constructing and deconstructing the gate theory of pain

Abstract

The gate theory of pain, published by Ronald Melzack and Patrick Wall in Science in 1965, was formulated to provide a mechanism for coding the nociceptive component of cutaneous sensory input. The theory dealt explicitly with the apparent conflict in the 1960s between the paucity of sensory neurons that responded selectively to intense stimuli and the well-established finding that stimulation of the small fibers in peripheral nerves is required for the stimulus to be described as painful. It incorporated recently discovered mechanisms of presynaptic control of synaptic transmission from large and small sensory afferents, which was suggested to "gate" incoming information depending on the balance between these inputs. Other important features included the convergence of small and large sensory inputs on spinal neurons that transmitted the sensory information to the forebrain as well as the ability of descending control pathways to affect the biasing established by the gate. The clarity of the model and its description gave this article immediate visibility, with numerous attempts made to test its various predictions. Although subsequent experiments and clinical findings have made clear that the model is not correct in detail, the general ideas put forth in the article and the experiments they prompted in both animals and patients have transformed our understanding of pain mechanisms.

Keywords: Dorsal horn; Dorsal root potentials; Gate theory; Nociceptor; Presynaptic inhibition; Substantia gelatinosa; TENS.

Figure 1

Negative (upward going) and positive (downward going) dorsal root potentials produced by stimulating large (A-) and small (C-) fibers. The diagram illustrates the dorsal root potential recording (R), and sural nerve stimulation (S). The square electrodes (+ and −) on the peripheral nerve illustrate the arrangement to produce selective anodal block of the large A-fibers that permitted the effects of C-fibers to be observed (from [50] with permission).

Figure 2

Arrangement of small and large fiber inputs to the SG in the dorsal horn. A. Sagittal view of the lumbar dorsal horn (laminae I to IV) modified from Figure 3 of [61]- with permission). The original figure was a schematic drawing of the cells observed in the superficial dorsal horn. Here we emphasize certain features of that schematic to illustrate the concepts used by Melzack and Wall in their elaboration of the Gate Theory. Large DRG axons (orange) run rostrocaudally in dorsal columns (Dors Fasc) and drop to below the SG to terminate on large cells in lamina IV (shown most ventrally). They also recurve dorsally and enter SG from the ventral surface. Small DRG axons (blue) run rostrocaudally in Lissauer’s tract (LISS Tract) and enter the SG (S GEL) from the dorsal surface. They also terminate on cells of lamina I. A single SG cell (green) is shown to project to other segments of SG via Lissauer’s tract; this cell does not project outside SG in keeping with the idea that SG is a modulatory system rather than a projecting system (but see text). Other SG cells in the original Szentagothai schematic are in background (gray). Note that SG is shown to be in laminae II and III; more recently this structure has been considered to be restricted to lamina II. B. Inputs to SG as illustrated in [45]. Here the SG is shown as a horizontal slab. Four sensory afferents are shown entering from the dorsal roots. Two large fibers (solid) curve around the slab and enter from the ventral surface. Two small fibers (dashed) enter from the dorsal surface. Lissauer’s tract (LT) is shown laterally as are 2 cells in deeper lamina of the dorsal horn. The inset illustrates the dorso- ventral location of the slab in cross section (dotted structure). Redrawn from [45], with permission). C. Recent analysis of inputs to and outputs from lamina II. In contrast to the Szentagothai picure, cells in lamina II terminate on projection neurons in laminae I and IV. Redrawn from [63], with permission.

Figure 3

The Gate Theory of Pain model published by Melzack and Wall [45]. Large (L) and small (S) sensory fibers excite T- (transmission) cells in the dorsal horn where they engage the “Action System”. However, they differ in their projections to cells of the SG. Large afferent fibers excite SG cells and elicit presynaptic inhibition of sensory inputs, both from small and large inputs. Small afferent fibers inhibit SG cells and remove presynaptic inhibition, in effect eliciting presynaptic facilitation. Thus the Gate will be open or closed depending on the balance between the large and small fiber input. Central control is envisioned as a descending system activated by rostral projections of large fiber input via the dorsal columns. Further details in the text. From [45], with permission.