33.1 Introduction

The pathophysiology of pain transmission and processing is complex and involves numerous peripheral and central components. Of course the physiological sensation of acute pain is an important protective response. Chronic pain no longer serves this physiological function. It is the result of plastic changes in the peripheral and central nervous system. As such, chronic pain can be considered a pathological disease state and not a symptom. In this chapter, we will briefly review the relevant anatomy of pain processing and the gate control theory, as well as discuss the differences between acute and chronic pain, nociceptive and neuropathic pain, and peripheral and central sensitization.

33.2 Pain Anatomy & The Gate Control Theory

Pain signals arise from free nerve endings and thermal receptors of the peripheral nervous system. It is transmitted by Aδ and C fibers, to the dorsal root ganglia, where the information is first processed. From the dorsal root ganglia, signals pass to the dorsolateral tract of Lissauer to synapse in the substantia gelatinosa of dorsal horn. Pain signals ultimately reach the brain through ascending pathways, most notably the anterior and lateral spinothalamic tracts, for cortical processing. Through different feedback mechanisms descending modulatory systems may alter these signals.

Acute pain protects the body from damaging stimuli. Chronic pain does not serve the same purpose. Can we understand how it comes about? Can we stop it from developing?

Much of our modern understanding of pain originates from the gate control theory of pain. The theory posits that interneurons within the substantia gelatinosa of the dorsal horns modulate pain signals before they are transmitted to the brain. ¹ This revolutionary idea powered the development of neuromodulation for chronic pain. Spinal cord stimulation works, yet, the concept behind it does not adequately explain why or how chronic pain develops. ²

33.3 Nociceptive and Neuropathic Pain

Nociceptive pain, or the detection of and response to noxious stimuli, refers to the peripheral pathway in which signals conveying non-neuronal tissue damage are transmitted to the central nervous system. ³ Primary afferent receptors, or nociceptors, are classified as somatic or visceral. Somatic nociceptors are located in cutaneous tissue, bone, joints and muscles, whereas visceral nociceptors are located in visceral structures and surrounding hollow organs. These primary afferents transmit signals to the dorsal horn of the spinal cord by two fiber types: Myelinated Aδ fibers conduct signals quickly and are responsible for pinprick sensation. Unmyelinated C fibers conduct signals slower. They signal burning, dull or itching pain. ⁴ Nociceptive information is then conducted to the brain via lateral and medial ascending pathways to reach the thalamus. The lateral thalamic relay projects to the somatosensory cortex and is involved in the sensory-discriminative component of pain, whereas the medial thalamic relay projects to the insula and cingulate cortex and is involved in the affective component of pain. ⁵

Neuropathic pain derives from damage to nervous system structures or the nerves themselves. As such, pathological processes such as vascular and autoimmune diseases, malignancies and infections can lead to the onset of neuropathic pain. ⁶ Lesions that produce neuropathic pain invariably involve nociceptive pathways, resulting in aberrant pain signaling to various pain centers in the absence of ongoing noxious stimuli. In response to nervous system injury, microglia become activated and release various pro-inflammatory cytokines that alter normal synaptic function, causing disorganized connectivity and the ectopic generation of action potentials. ⁷