Last updated: Thu, Jun 22, 2017
The presently known signaling pathways [in the spine] probably just reflect the tip of an enormous iceberg of spinal signaling molecules contributing to the pathogenesis of hyperalgesia and allodynia.1
We've seen in this section that the spinal processing of both nociceptive and innocuous sensory signals is complex. The system provides reflexive responses to immediate injury (flexor and withdrawal reflexes), plus different responses to cutaneous and deep tissue injury that seem to be biologically useful. Spinal cord mechanisms that allow it to adjust its sensitivity are part of these responses. We've also seen that in unusual and abnormal circumstances (such as peripheral nerve injury or inflammation) these same mechanisms can lead to extended pain that seems not to provide biological benefit.
About one-third of the neurons in the spinal cord are inhibitory—that is, their synapses emit trasnsmitters that tend to inhibit the post-synaptic neurons. Inhibition in the cord is also affected by signals from descending inhibitory neurons, which is part of the story of the next chapter. Inhibition in the dorsal horn serves five important functions. When these fail to work well or encounter unusual stresses, it causes problems.2
| Function | How | Why | Result of failure |
|---|---|---|---|
| Muting | Continual (tonic) inhibition of ascending nociceptive projection neurons | These neurons fire spontaneously if not inhibited | Spontaneous pain without stimulus |
| Attenuation | Tonic inhibition plus feedback and feedforward inhibition especially during noxious stimulation | Spinal nociceptive neurons otherwise become overactive | Hyperalgesia |
| Limiting | Tonic inhibition plus feedback and feedforward inhibition especially during noxious stimulation | Input from physically adjacent neurons can cause input to spread up and down the spine or side-to-side | Radiating and referred pain |
| Separating | Inhibition of excitatory interneurons that can link innocuous A-beta input to nociceptive pathways | Connections between innocuous and nociceptive signals exist that must be kept silent | Allodynia |
| Preventing | Both presynaptic and postsynaptic inhibition reduce the potential for intrinsic plasticity of spinal neurons | Inhibition helps to prevent the development of a "memory trace " in excitatory spinal synapses | Chronic pain |
In the following section we'll extend this chapter's look at acute pain to the level of the brain.