From brainstem nuclei, impulses "descend" onto the spinal cord and influence the transmission of pain signals at the dorsal horn.18,19,20 The periaqueductal gray (PAG) matter is a key region for descending inhibition. It receives inputs from the hypothalamus, cortical regions, and the limbic system and projects to the rostral ventromedial medulla (RVM), which includes several subnuclei. Neurons in RVM then project along the dor-solateral funiculus (DLF) to the dorsal horn. OFF cells of RVM exert descending inhibition of nociception, but ON cells facilitate nociceptive mechanisms at the spinal dorsal horn. Spinobulbospinal loops are significant in setting the gain of spinal processing.19
A particular form of descending inhibition of wide dynamic range neurons is the diffuse noxious inhibitory controls (DNIC). When a strong noxious stimulus is applied to a given body region, nociceptive neurons with input from that body region send impulses to structures located in the caudal medulla (caudal to RVM) and this triggers a centrifugal inhibition (DNIC) of nociceptive wide dynamic range neurons located throughout the
Most spinal cord neurons with joint and muscle input are tonically inhibited by descending inhibitory systems that modulate spinal cord activity.81,110 These neurons are also inhibited by DNIC.109 Tonic descending inhibition,110 as well as DNIC,109,111 are increased during acute inflammation, but may be normalized in the chronic stage of inflammation.111,112 Interestingly, inhibition is mainly observed on neurons with input from the inflamed region (thus attenuating primary hyperalgesia), but processing in neurons with input from neighboring tissues may rather be enhanced, thus facilitating secondary hyperalgesia.19
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