Dorsal Horn Pain Mechanisms

Abstract

<p>The spinal dorsal horn and its equivalent structure in the brainstem constitute the first sites of synaptic integration in the pain pathway. A huge body of literature exists on alterations in spinal nociceptive signal processing that contribute to the generation of exaggerated pain states and hence to what is generally known as “central sensitization.” Such mechanisms include changes in synaptic efficacy or neuronal excitability, which can be evoked by intense nociceptive stimulation or by inflammatory or neuropathic insults. Some of these changes cause alterations in the functional organization of dorsal horn sensory circuits, leading to abnormal pathological pain sensations. This article reviews the present state of this knowledge. It does not cover the contributions of astrocytes and microglia in detail as their functions are the subject of a separate chapter.</p>

Sex differences in central inflammatory pain sensitization are associated with differential expression of glycine receptors and GLP-1 at the spinal cord

“…Furthermore, our results showed that both males and females had increased α3GlyR. This subunit is expressed in the dorsal horn spinal cord where the pain signaling is integrated [21]. Previous report demonstrated that α3GlyRs underlies inflammatory central pain sensitization [5].…”

Microglia and Inhibitory Circuitry in the Medullary Dorsal Horn: Laminar and Time-Dependent Changes in a Trigeminal Model of Neuropathic Pain

“…Although some authors proposed that neuropathic pain was primarily due to the downregulation of inhibitory transmission, with microglia activation being just a secondary phenomenon [ 40 ], other studies hold that nerve injury initiates a cascade of events involved in the development and maintenance of neuropathic pain [ 12 , 62 , 63 ]. Summarily (see [ 17 , 64 ], for recent reviews), microglia is activated by cytokines and chemokines released by injured peripheral nerve fibers, which increases the synthesis and membrane insertion of several purinergic receptors of the P2X ion-channel family. ATP released from primary afferents, the microglia itself, and local interneurons activates P2X4 receptors, resulting in the release within minutes of BDNF [ 65 ] which binds to its high-affinity receptor trkB.…”