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. 2006:81:103-25.
doi: 10.1016/S0072-9752(06)80013-8.

Chapter 9 The dorsal horn and hyperalgesia

Karin N Westlund

Chapter 9 The dorsal horn and hyperalgesia

Karin N Westlund. Handb Clin Neurol. 2006.
No abstract available

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Figures

Fig. 9.1
Fig. 9.1
Hardy and colleagues proposed that in the case of sustained noxious stimulation, primary and secondary hyperalgesia were the result of the involvement of increasingly larger pools of neurons which become activated by released neuroactive substances. (From Hardy et al., 1967.)
Fig. 9.2
Fig. 9.2
Hardy and colleagues proposed that primary afferents activate interneuronal networks in the dorsal horn which activate other neurons in the spinal cord and provide the secondary hyperalgesia sensation in the adjacent cutaneous areas. (From Hardy et al., 1967.)
Fig. 9.3
Fig. 9.3
The dorsal horn neurochemical microenvironment is characterized by an overabundance of neurochemical mediators and neurotransmitters which are not successfully inactivated or taken back up in prolonged states of activation. Neurochemical profiles demonstrated in various animal models vary but all have in common an increase in dorsal horn dynorphin believed to contribute to the sensitized nociceptive state. (GLU: glutamate; Sub P: substance P; CGRP: calcitonin gene-related peptide; PKCγ: protein kinase C gamma; NOS: nitric oxide synthase; GABA: gamma-aminobutyric acid; SHT: S-hydroxytryptamine.)
Fig. 9.4
Fig. 9.4
After an initial insult or injury, there is an initial spiking release of specific neurotransmitters at the time of injury followed by a slow sustained wave of release. During this same time there is a slowly evolving and protracted period of increased sensitization that arises and persists for a variable amount of time dependent on factors such as the increased release of glutamate into the neurochemical microenvironment of the dorsal horn varying with the type of inflammatory injury. Cutaneous administration of capsaicin or formalin produces a greatly compressed time frame for the release of neurotransmitters and the development of hyperalgesic responses over minutes. Hindpaw and knee joint injections of the irritants, kaolin and carrageenan, produce sensitization over several hours. The time course for development of hyperalgesia due to complete Freund’s adjuvant is greatly protracted over days to weeks.
Fig. 9.5
Fig. 9.5
Sluka and Westlund proposed a neurogenic amplification loop that increases afferent nerve input to the dorsal horn and hyperalgesic responses of dorsal horn neurons, and triggers dorsal root reflex (DRR) firing back out of the nerves to the periphery. The self-perpetuating vicious circle produces persistence of hyperalgesic pain states and maintains inflammation in the periphery. The dorsal horn circuitry involves non-NMDA and GABAA receptor activation and primary afferent depolarization, and impacts NMDA-mediated ascending spinothalamic tract output. (Modified from Sluka et al., 1995b.)
Fig. 9.6
Fig. 9.6
Descending systems impact the nociceptive processes in the spinal cord. Activation of brainstem regions by ascending nociceptive input from the spinal cord produces complex interactive events in the brainstem that result in a shift in the balance of the integrated excitatory and inhibitory output that arrives in descending projections to the spinal cord dorsal horn. Descending inhibition serves to damp the dorsal horn activation state while descending facilitation will shift the balance to a higher activation state. During sustained nociceptive states, descending facilitation shifts the balance of the spinal activation, conveying sensitivity to previously innocuous stimuli. The more diffuse nature of the descending system innervation of the spinal cord participates in the expansion of the sensitization to additional spinal levels bilaterally. Descending facilitation impacts dorsal horn hyperalgesia through dorsolateral funicular axonal pathways carrying serotonin (5HT) and cholecystokinin (CCK). Descending facilitatory pathways originate in the periaqueductal gray (PAG) and the rostral ventromedial medulla (RVM) and travel in the dorsolateral funiculus of the spinal cord through its length. Descending noradrenergic (NA) inhibitory pathways that impact alpha 2-type receptors in the spinal cord originate from noradrenergic cell groups A5–A7 in the pons and are situated ventrolaterally through the length of the spinal cord.
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