Myelinated Skin Sensory Neurons Project Extensively throughout Adult Mouse Substantia Gelatinosa

Abstract

The substantia gelatinosa (SG) of the dorsal horn of the spinal cord is a recipient zone for unmyelinated sensory neurons in adults. Recent studies of the central anatomy of physiologically identified skin sensory neurons in neonatal mice have shown that this region also receives substantial inputs from a variety of myelinated afferents. The present experiments were performed to determine whether these neonatal inputs represent a transient phenotype that retracts from the SG. Studies were conducted in an in vivo spinal cord preparation from adult mice; thoracic levels were targeted to facilitate comparisons with previous in vitro findings. We show that the SG continues to receive substantial projections from myelinated skin sensory neurons throughout life. A large population of myelinated nociceptors conducting in the upper A␦ and low A␤ range maintained extensive projections throughout all areas of the SG well into adulthood; the latter gave rise to dorsally recurving "flame"-shaped arbors extending into the marginal layer that were identical to afferents described in neonates and after nerve injury in adult rats. Furthermore, exquisitely sensitive down hair follicle afferents projected throughout the inner half of the SG (i.e., lamina IIi) and sent dense clusters of terminals well into the outer SG (IIo), where they intermingled with those of unmyelinated nociceptors. Arguments are presented that the SG likely plays a predominant role in tactile processing under normal conditions, but that this role switches rapidly to nociceptive-only during environmental exigencies imposed by temperature extremes.

Genetic Identification of an Expansive Mechanoreceptor Sensitive to Skin Stroking

“…In the spinal cord, these CFP + neurons project within lamina II iv to lamina IV, partially overlapping with the PKCγ + interneurons of lamina II iv and III but not with IB4 + terminals in lamina II id (Figure 2A-2B). These spinal cord terminations overlap with, but are slightly more dorsal than those of other Aβ-LTMR subtypes, including Aβ RA-LTMRs (Luo et al, 2009) and Aβ SA1-LTMRs that innervate laminar III to V (Figure 2C-2D), and they resemble the spinal cord innervation patterns of a subset of myelinated nociceptors (Boada and Woodbury, 2008). Furthermore, CFP + circumferential ending neurons have central projections that terminate in the gracile and the dorsal cuneate nuclei of the DCN (Figure 2F-2G), but are excluded from the ventral cuneate and external cuneate nuclei (Figure 2E-2G), similar to Aβ RA-LTMRs (Luo et al, 2009).…”

Low-Threshold Primary Afferent Drive onto GABAergic Interneurons in the Superficial Dorsal Horn of the Mouse

“…Nevertheless, we cannot exclude the possibility that additional innocuous cutaneous information is carried by D hair (Aδ) fibers or LT mechanosensitive C fibers (Burgess and Perl, 1967; Lynn and Carpenter, 1982; Sugiura et al, 1986; Traub and Mendell, 1988; Ritter and Mendell, 1992; Koltzenburg et al, 1997; Woodbury et al, 2001; Lu and Perl, 2003; Boada and Woodbury, 2008). However, we probably did not misclassify these as Aβ fibers, because there is a distinction between thresholds for cutaneous vs. electrical stimuli.…”

“…Afferents with low mechanical, but high electrical thresholds may nevertheless contribute to the excitatory pathway producing allodynia in the disinhibited dorsal horn. In addition, some of our Aβ fiber input may be from nociceptors (Koerber et al, 1988; Ritter and Mendell, 1992; Djouhri et al, 1998; Djouhri and Lawson, 2004; Boada and Woodbury, 2008), although the majority of Aβ fibers selectively carry innocuous touch sensation (Djouhri and Lawson, 2004). …”

Primary Afferent Projections to the Spinal Cord

“…Group Ib fibers from Golgi tendon organs terminate in laminae 6-7, and group II fibers in laminae 4-7 and 9 (Brown, 1981). Hair follicle afferents project throughout the inner half of lamina 2 (lamina 2i) and send dense clusters of terminals into the outer lamina 2 (lamina 2o) where they intermingle with fibers of unmyelinated nociceptors (Boada and Woodbury, 2008). Some of these afferents descend through laminae 1-3 to laminae 4-5, then curve back to end in the superficial part of lamina 4 and 3 (Brown et al, 1977).…”