Chemical activation of C1-C2 spinal neurons modulates intercostal and phrenic nerve activity in rats

Chemical activation of upper cervical spinal neurons modulates activity of thoracic respiratory interneurons in rats. The aim of the present study was to examine the effects of chemical activation of C(1)-C(2) spinal neurons on thoracic spinal respiratory motor outflows. Electroneurograms of left phrenic (n = 23) and intercostal nerves (ICNs, n = 93) between T(3) and T(8) spinal segments were recorded from 36 decerebrated, vagotomized, paralyzed, and ventilated male rats. To activate upper cervical spinal neurons, glutamate pledgets (1 M, 1 min) were placed on the dorsal surface of the C(1)-C(2) spinal cord. Glutamate on C(1)-C(2) increased ICN tonic activity in 56/59 (95%) ICNs. The average maximal tonic activity of ICN was increased by 174% (n = 59). After spinal transection at rostral C(1), glutamate on C(1)-C(2) still increased ICN tonic activity in 33/35 ICNs. However, the effects of C(1)-C(2) glutamate on ICN phasic activity were highly variable, with observations of augmentation or suppression of both inspiratory and expiratory discharge. C(1)-C(2) glutamate augmented the average amplitude of phrenic burst by 20%, whereas the increases in amplitude of ICN inspiratory activity, when they occurred, averaged 120%. The burst rate of phrenic nerve discharge was decreased from 34.2 +/- 1.6 to 26.3 +/- 2.0 (mean +/- SE) breaths/min during C(1)-C(2) glutamate. These data suggested that upper cervical propriospinal neurons might play a role in descending modulation of thoracic respiratory and nonrespiratory motor activity.     

C2 spinal cord stimulation induces dynorphin release from rat T4 spinal cord: potential modulation of myocardial ischemia-sensitive neurons

During myocardial ischemia, the cranial cervical spinal cord (C1-C2) modulates the central processing of the cardiac nociceptive signal. This study was done to determine 1) whether C2 SCS-induced release of an analgesic neuropeptide in the dorsal horn of the thoracic (T4) spinal cord; 2) if one of the sources of this analgesic peptide was cervical propriospinal neurons, and 3) if chemical inactivation of C2 neurons altered local T4 substance P (SP) release during concurrent C2 SCS and cardiac ischemia. Ischemia was induced by intermittent occlusion of the left anterior descending coronary artery (CoAO) in urethane-anesthetized Sprague-Dawley rats. Release of dynorphin A (1-13), (DYN) and SP was determined using antibody-coated microprobes inserted into T4. SCS alone induced DYN release from laminae I-V in T4, and this release was maintained during CoAO. C2 injection of the excitotoxin, ibotenic acid, prior to SCS, inhibited T4 DYN release during SCS and ischemia; it also reversed the inhibition of SP release from T4 dorsal laminae during C2 SCS and CoAO. Injection of the kappa-opioid antagonist, nor-binaltorphimine, into T4 also allowed an increased SP release during SCS and CoAO. CoAO increased the number of Fos-positive neurons in T4 dorsal horns but not in the intermediolateral columns (IML), while SCS (either alone or during CoAO) minimized this dorsal horn response to CoAO alone, while inducing T4 IML neuronal recruitment. These results suggest that activation of cervical propriospinal pathways induces DYN release in the thoracic spinal cord, thereby modulating nociceptive signals from the ischemic heart.     

Increased spinal monoamine concentrations after chronic thoracic dorsal rhizotomy in goats.

In goats, bilateral thoracic dorsal rhizotomy (TDR) causes severe ventilatory failure during exercise, followed by progressive functional recovery. We investigated spinal neurochemical changes associated with TDR and/or functional recovery by measuring spinal concentrations of the monoamines serotonin (5-HT), norepinephrine, and dopamine via HPLC. Changes in 5-HT and calcitonin gene-related peptide were visualized with immunohistochemistry. Goat spinal cords were compared 4-15 mo after TDR from T(2) to T(12) (n = 7) with sham-operated (n = 4) or unoperated controls (n = 4). TDR increased the concentration of cervical 5-HT (C(5)-C(6); 122% change), caudal thoracic norepinephrine (T(7)-T(11); 53% change), and rostral thoracic dopamine (T(3)-T(6); 234% change). TDR increased 5-HT-immunoreactive terminal density (dorsal and ventral horns) and nearly eliminated calcitonin gene-related peptide immunoreactivity in the superficial laminae of the dorsal horn in rostral thoracic segments; both effects became less pronounced in caudal thoracic segments. Thus TDR elevates monoamine concentrations in discrete spinal regions, including possible compensatory changes in descending serotonergic inputs to spinal segments not directly affected by TDR (i.e., cervical) but associated with functionally related motor nuclei (i.e., phrenic nucleus).     

c-Fos expression in rat brain stem and spinal cord in response to activation of cardiac ischemia-sensitive afferent neurons and electrostimulatory modulation

The purpose of this study was to identify central neuronal sites activated by stimulation of cardiac ischemia-sensitive afferent neurons and determine whether electrical stimulation of left vagal afferent fibers modified the pattern of neuronal activation. Fos-like immunoreactivity (Fos-LI) was used as an index of neuronal activation in selected levels of cervical and thoracic spinal cord and brain stem. Adult Sprague-Dawley rats were anesthetized with urethane and underwent intrapericardial infusion of an "inflammatory exudate solution" (IES) containing algogenic substances that are released during ischemia (10 mM adenosine, bradykinin, prostaglandin E2, and 5-hydroxytryptamine) or occlusion of the left anterior descending coronary artery (CoAO) to activate cardiac ischemia-sensitive (nociceptive) afferent fibers. IES and CoAO increased Fos-LI above resting levels in dorsal horns in laminae I-V at C2 and T4 and in the caudal nucleus tractus solitarius. Dorsal rhizotomy virtually eliminated Fos-LI in the spinal cord as well as the brain stem. Neuromodulation of the ischemic signal by electrical stimulation of the central end of the left thoracic vagus excited neurons at the cervical and brain stem level but inhibited neurons at the thoracic spinal cord during IES or CoAO. These results suggest that stimulation of the left thoracic vagus excites descending inhibitory pathways. Inhibition at the thoracic spinal level that suppresses the ischemic (nociceptive) input signal may occur by a short-loop descending pathway via signals from cervical propriospinal circuits and/or a longer-loop descending pathway via signals from the nucleus tractus solitarius.     

Fictive locomotion and scratching inhibit dorsal horn neurons receiving thin fiber afferent input

In decerebrate paralyzed cats, we examined the effects of two central motor commands (fictive locomotion and scratching) on the discharge of dorsal horn neurons receiving input from group III and IV tibial nerve afferents. We recorded the impulse activity of 74 dorsal horn neurons, each of which received group III input from the tibial nerve. Electrical stimulation of the mesencephalic locomotor region (MLR), which evoked fictive static contraction or fictive locomotion, inhibited the discharge of 44 of the 64 dorsal horn neurons tested. The mean depth from the dorsal surface of the spinal cord of the 44 neurons whose discharge was inhibited by MLR stimulation was 1.77 +/- 0.04 mm. Fictive scratching, evoked by topical application of bicuculline to the cervical spinal cord and irritation of the ear, inhibited the discharge of 22 of the 29 dorsal horn neurons tested. Fourteen of the twenty-two neurons whose discharge was inhibited by fictive scratching were found to be inhibited by MLR stimulation as well. The mean depth from the dorsal surface of the cord of the 22 neurons whose discharge was inhibited by fictive scratching was 1.77 +/- 0.06 mm. Stimulation of the MLR or the elicitation of fictive scratching had no effect on the activity of 22 dorsal horn neurons receiving input from group III and IV tibial nerve afferents. The mean depth from the dorsal surface of the cord was 1.17 +/- 0.07 mm, a value that was significantly (P < 0.05) less than that for the neurons whose discharge was inhibited by either MLR stimulation or fictive scratching. We conclude that centrally evoked motor commands can inhibit the discharge of dorsal horn neurons receiving thin fiber input from the periphery.     

福尔马林致痛后大鼠中脑导水管周围灰质甲啡肽及脊髓背角P物质含量的变化

本文用免疫组化方法结合计算机图像处理技术观察大鼠后脚掌皮下注射福尔马林后脊髓背角Ｐ物质免疫阳性反应（ＳＰＬＩ）变化的节段性分布及中脑导水管周围灰质（ＰＡＧ）内甲啡肽样免疫阳性反应（ＭＥＬＩ）的变化。结果显示,注射福尔马林后,脊髓腰段（Ｌ１－２,Ｌ４－５）背角ＳＰＬＩ显著增强（Ｐ＜．０５）,３０ｍｉｎ组与６０ｍｉｎ组相比较无显著变化（Ｐ＞０．０５）;胸脊髓（Ｔ８）无显著变化（Ｐ＞０．０５）;颈脊髓背角ＳＰＬＩ有增强趋势（０．０５＜Ｐ＜０．１）;ＰＡＧ中ＭＥＬＩ减弱,腹外侧部３０ｍｉｎ组比６０ｍｉｎ组变化更大（Ｐ＜０．０５）。ＰＡＧ中ＭＥＬＩ与脊髓背角ＳＰＬＩ变化的时相关系提示福尔马林致痛引起的脊髓背角Ｐ物质的增多可能与ＰＡＧ中甲啡肽及阿片受体活动有关。     

Attenuation of phrenic motor discharge by phrenic nerve afferents

Short latency phrenic motor responses to phrenic nerve stimulation were studied in anesthetized, paralyzed cats. Electrical stimulation (0.2 ms, 0.01-10 mA, 2 Hz) of the right C5 phrenic rootlet during inspiration consistently elicited a transient reduction in the phrenic motor discharge. This attenuation occurred bilaterally with an onset latency of 8-12 ms and a duration of 8-30 ms. Section of the ipsilateral C4-C6 dorsal roots abolished the response to stimulation, thereby confirming the involvement of phrenic nerve afferent activity. Stimulation of the left C5 phrenic rootlet or the right thoracic phrenic nerve usually elicited similar inhibitory responses. The difference in onset latency of responses to cervical vs. thoracic phrenic nerve stimulation indicates activation of group III afferents with a peripheral conduction velocity of approximately 10 m/s. A much shorter latency response (5 ms) was evoked ipsilaterally by thoracic phrenic nerve stimulation. Section of either the C5 or C6 dorsal root altered the ipsilateral response so that it resembled the longer latency contralateral response. The low-stimulus threshold and short latency for the ipsilateral response to thoracic phrenic nerve stimulation suggest that it involves larger diameter fibers. Decerebration, decerebellation, and transection of the dorsal columns at C2 do not abolish the inhibitory phrenic-to-phrenic reflex.     

Distribution of alpha 1 subunit isoform of (Na,K)-ATPase in the rat spinal cord

Three isoforms of the alpha subunit of (Na,K)-ATPase have been identified in the rat central nervous system. Using a probe specific for the alpha 1 isoform, mRNA levels were measured from five sections of the rat spinal cord using slot blot techniques. Assigning a value of 1 to the slope obtained from the cervical section, the upper thoracic section was 2.6 times higher; the midthoracic section was 4.5 times higher; the lower thoracic section was 2.6 times higher; and the lumbar section was 1.7 times higher. The results suggest that alpha 1 isoform mRNA levels are not uniform throughout the spinal cord. In situ hybridization techniques showed that alpha 1 isoform mRNA was diffusely abundant in glial and central canal ependymal cells, while labeled neurons were localized exclusively in lateraily located anterior horn neurons in cervical, thoracic, and lumbar segments and in ventromedial neurons in mid-thoracic spinal cord. Also, dorsal root ganglia neurons were extensively labeled at all segments.Special issue dedicated to Dr. Bernard W. Agranoff.     

Organization of motoneurons innervating the axial musculature of the brown caiman (Caiman crocodilus fuscus)

The primary divisions of the spinal nerve in the brown caiman characteristically show the following features: (1) the medial ramus was lies in the thoraco-lumbar and caudal regions, and (2) the first cervical and hypoglossal nerves form a single nerve complex from which the ventral and dorsal rami extend. Intramuscular injections of horseradish peroxidase (HRP) established the positions of motoneurons whose axons followed the primary rami. In the ventral horn of the thoracic and caudal spinal cord, the motoneurons of the medial ramus lie ventrally. These motoneurons lie between the epaxial and hypaxial motoneurons. At the spinomedullary junction, the pools of motoneurons innervating the infrahyoid, lingual, and dorsal muscles have a somatotopic organization similar to that observed in the thoraco-lumbar and caudal regions. Thus clear somatotopic organization of the motoneurons that innervate the axial musculature exists at all spinal levels. © 1994 Wiley-Liss, Inc.     

Left vagal stimulation induces dynorphin release and suppresses substance P release from the rat thoracic spinal cord during cardiac ischemia

Electrostimulatory forms of therapy can reduce angina that arises from activation of cardiac nociceptive afferent fibers during transient ischemia. This study sought to determine the effects of electrical stimulation of left thoracic vagal afferents (C(8)-T(1) level) on the release of putative nociceptive [substance P (SP)] and analgesic [dynorphin (Dyn)] peptides in the dorsal horn at the T(4) spinal level during coronary artery occlusion in urethane-anesthetized Sprague-Dawley rats. Release of Dyn and SP was measured by using antibody-coated microprobes. While Dyn and SP had a basal release, occlusion of the left anterior descending coronary artery only affected SP release, causing an increase from lamina I-VII. Left vagal stimulation increased Dyn release, inhibited basal SP release, and blunted the coronary artery occlusion-induced release of SP. Dyn release reflected activation of descending pathways in the thoracic spinal cord, because vagal afferent stimulation still increased the release of Dyn after bilateral dorsal rhizotomy of T(2)-T(5). These results indicate that electrostimulatory therapy, using vagal afferent excitation, may induce analgesia, in part, via inhibition of the release of SP in the spinal cord, possibly through a Dyn-mediated neuronal interaction.     

Persistent At-Level Thermal Hyperalgesia and Tactile Allodynia Accompany Chronic Neuronal and Astrocyte Activation in Superficial Dorsal Horn following Mouse Cervical Contusion Spinal Cord Injury

In humans, sensory abnormalities, including neuropathic pain, often result from traumatic spinal cord injury (SCI). SCI can induce cellular changes in the CNS, termed central sensitization, that alter excitability of spinal cord neurons, including those in the dorsal horn involved in pain transmission. Persistently elevated levels of neuronal activity, glial activation, and glutamatergic transmission are thought to contribute to the hyperexcitability of these dorsal horn neurons, which can lead to maladaptive circuitry, aberrant pain processing and, ultimately, chronic neuropathic pain. Here we present a mouse model of SCI-induced neuropathic pain that exhibits a persistent pain phenotype accompanied by chronic neuronal hyperexcitability and glial activation in the spinal cord dorsal horn. We generated a unilateral cervical contusion injury at the C5 or C6 level of the adult mouse spinal cord. Following injury, an increase in the number of neurons expressing ΔFosB (a marker of chronic neuronal activation), persistent astrocyte activation and proliferation (as measured by GFAP and Ki67 expression), and a decrease in the expression of the astrocyte glutamate transporter GLT1 are observed in the ipsilateral superficial dorsal horn of cervical spinal cord. These changes have previously been associated with neuronal hyperexcitability and may contribute to altered pain transmission and chronic neuropathic pain. In our model, they are accompanied by robust at-level hyperaglesia in the ipsilateral forepaw and allodynia in both forepaws that are evident within two weeks following injury and persist for at least six weeks. Furthermore, the pain phenotype occurs in the absence of alterations in forelimb grip strength, suggesting that it represents sensory and not motor abnormalities. Given the importance of transgenic mouse technology, this clinically-relevant model provides a resource that can be used to study the molecular mechanisms contributing to neuropathic pain following SCI and to identify potential therapeutic targets for the treatment of chronic pathological pain.     

The effect of galanin on wide-dynamic range neuron activity in the spinal dorsal horn of rats

The present study investigated the effect of galanin on wide-dynamic range (WDR) neuron activity in the dorsal horn of the spinal cord of rats. The evoked discharge of WDR neurons was elicited by transdermic electrical stimulation applied on the ipsilateral hindpaw of rats. Galanin was administered directly on the spinal dorsal surface of L3-L5. The evoked discharge frequency of the WDR neurons decreased significantly after the administration of galanin and the effect lasted for more than 30 min. Furthermore, the inhibitory effect of galanin on the evoked discharge frequency of WDR neurons was blocked by following administration of the galanin antagonist galantide, indicating that the inhibitory effect of galanin on the activity of WDR neurons was induced by activating galanin receptors in the dorsal horn of the spinal cord. The results suggest that galanin has an inhibitory role in the transmission of presumed nociceptive information in the dorsal horn of the spinal cord in rats.     

Avian pancreatic polypeptide (APP) immunoreactive neurons in the spinal cord and spinal trigeminal nucleus

Using indirect immunofluorescence technique, avian pancreatic polypeptide (APP) immunoreactive cell bodies and fibres have been observed in the superficial laminae of the dorsal horn of the spinal cord and of the spinal trigeminal nucleus. Fibres were also seen in the ventral horns, in low numbers at the cervical and thoracic levels and in high numbers at the lower lumbar and upper sacral levels. Neither total cord transection, nor dorsal rhizotomy, nor capsaicin treatment seemed to affect the APP systems described above. The present findings suggest that an APP-like peptide may be involved in processing of sensory information at the level of the first relay station.     

The distribution and origin of VIP in the spinal cord of six mammalian species

The distribution of VIP-immunoreactivity was studied in the spinal cord and dorsal root ganglia of 6 mammalian species. Immunoreactive fibres and cell bodies were most apparent in the dorsal horn, dorsolateral funiculus, intermediolateral cell columns and the area around the central canal. The distribution of VIP immunoreactivity was similar in all species studied, mouse, rat, guinea pig, cat, horse and the marmoset monkey. There were fewer VIP fibres in the dorsal horn of cervical and thoracic segments than in lumbosacral segments. Using radioimmunoassay this gradient increase was quantitatively most marked in the sacral spinal cord of the cat. In dorsal root ganglia few nerve cell bodies but numerous fibres were present. A dual origin for VIP in the spinal cord is suggested: (A) Extrinsic, from dorsal root afferent fibres since immunoreactivity was decreased in dorsally rhizotomized animals (cats and rats) and in capsaicin pretreated rats (microinjection of dorsal root ganglia). (B) From local cell bodies intrinsic to the spinal cord which became visible after colchicine pretreatment of rats.     

Oxytocin prevents neuronal network pain-related changes on spinal cord dorsal horn in vitro

Recently, oxytocin (OT) has been studied as a potential modulator of endogenous analgesia by acting upon pain circuits at the spinal cord and supraspinal levels. Yet the detailed action mechanisms of OT are still undetermined. The present study aimed to evaluate the action of OT in the spinal cord dorsal horn network under nociceptive-like conditions induced by the activation of the N-methyl-d-aspartate (NMDA) receptor and formalin injection, using calcium imaging techniques. Results demonstrate that the spontaneous Ca²⁺-dependent activity of the dorsal horn cells was scarce, and the coactivity of cells was mainly absent. When NMDA was applied, high rates of activity and coactivity occurred in the dorsal horn cells; these rates of high activity mimicked the activity dynamics evoked by a neuropathic pain condition. In addition, although OT treatment increased activity rates, it was also capable of disrupting the conformation of coordinated activity previously consolidated by NMDA treatment, without showing any effect by itself. Altogether, our results suggest that OT globally prevents the formation of coordinated patterns previously generated by nociceptive-like conditions on dorsal horn cells by NMDA application, which supports previous evidence showing that OT represents a potential therapeutic alternative for the treatment of chronic neuropathic pain.     

Inducible Prrxl1-CreER(T2) recombination activity in the somatosensory afferent pathway

Prrxl1-CreER(T2) transgenic mice expressing tamoxifen-inducible Cre recombinase were generated by modifying a Prrxl1-containing BAC clone. Cre recombination activity was examined in Prrxl1-CreER(T2); Rosa26 reporter mice at various embryonic and postnatal stages. Pregnant mice were treated with a single dose of tamoxifen at embryonic day (E) 9.5 or E12.5, and X-gal staining was performed 2 days later. Strong X-gal staining was observed in the somatosensory ganglia (e.g., dorsal root and trigeminal ganglia) and the first central sites for processing somatosensory information (e.g., spinal dorsal horn and trigeminal nerve-associated nuclei). When tamoxifen was administered at postnatal day (P) 20 or in adulthood (P120), strong Cre recombination activity was present in the primary somatosensory ganglia, while weak Cre recombination activity was found in the spinal dorsal horn, mesencephalic trigeminal nucleus, principal sensory trigeminal nucleus, and spinal trigeminal nucleus. This mouse line provides a useful tool for exploring genes' functions in the somatosensory system in a time-controlled way.     

异丙酚对正常大鼠脊髓背角感觉神经元反应性的抑制作用

脊髓背角感觉神经元不仅在感觉信息的传递和调节中起到重要作用,也是各种内源性和外源性药物的作用靶位.为了解静脉麻醉剂异丙酚是否对背角感觉神经元的反应性具有调节作用,本实验采用在体单细胞胞外记录技术,观察了脊髓背表面直接滴注0.5 μmol异丙酚对戊巴比妥钠麻醉大鼠脊髓背角广动力域(WDR)神经元和低阈值机械感受型(LTM)神经元反应性的影响.实验发现,异丙酚能抑制背角WDR神经元由施加于外周感受野伤害性热刺激(45、47、49和53℃,15 s)和夹捏机械刺激(10 s)诱发的反应性,与DMSO对照组比较具有显著性统计学差异(P＜0.05);同样,异丙酚对非伤害性机械刺激诱发的WDR或LTM神经元的反应性也具有显著的抑制作用(P＜0.05).本结果提示,异丙酚可直接作用于正常大鼠脊髓背角神经元,对由非伤害性和伤害性纤维介导的神经元反应性均产生抑制作用,因此异丙酚的脊髓抗伤害作用可能不是特异性的.     

Lamination of spinal cells projecting to the zona incerta of rats

In this study, the lamination patterns of spinal cells projecting to the zona incerta (ZI), intralaminar nuclei and ventral posterior nucleus of the thalamus have been explored. Injections of cholera toxin subunit B or latex beads were made into the ZI, intralaminar and ventral posterior nuclei of Sprague Dawley rats. The brain and spinal cord were then aldehyde fixed and processed using standard methods. Our results show two major findings. First, after injections into the ZI, there is a distinct pattern of lamination of labelled cells in the spinal cord, a pattern that changes across the different levels. At cervical levels, labelled cells are located within the medial region of the deep dorsal horn, while at lumbar and sacral levels, they are found in the intermediate grey matter. These results are similar to those seen after injections into the intralaminar or ventral posterior nuclei, except that in the latter cases, more labelled cells are located in the superficial laminae of the dorsal horn, particularly from the ventral posterior nucleus. Second, the ZI is not associated uniformly with all spinal levels; labelling is heaviest at cervical and lightest at thoracic levels. From each thalamic injection site, labelling is noted on both sides of the spinal cord, with a clear contralateral predominance. In conclusion, the results indicate that the ZI receives a distinct set of spinal projections principally from the cervical level. The particular pattern of lamination of spinal cells projecting to the ZI suggests that the type of information relayed is from deep somatic and/or visceral structures, and probably nociceptive in nature.     

Innervation of the dermatomes in the neck of the mouse

The dorsal rami of the cervical and thoracic spinal nerves were investigated using both the in situ cholinesterase staining technique and cholinesterase staining on serial sections of plastic-embedded embryos. In most cases only the dorsal rami of the 2nd to 5th cervical spinal nerve possess cutaneous branches. The area innervated by the cutaneous branch of the dorsal ramus of the 5th spinal nerve borders on an area innervated by the cutaneous branch of the dorsal ramus of the 1st thoracic spinal nerve. The dorsal rami of the cervical spinal nerves 6-8 show no cutaneous branches. Therefore the gap in the series of the dorsal cutaneous branches is due only to the middle part of the nerves of the brachial plexus, which range from the 5th cervical nerve to the 1st thoracic nerve.     

Distribution of dipeptidyl peptidase II (Dpp II) in rat spinal cord

The histochemical localization of dipeptidyl peptidase II (Dpp II; E.C. 3.4.14.2) activity was demonstrated at the light microscope level in the rat spinal cord. Prominent staining was observed in motoneurons of the ventral horn and in medium to large neurons in the deep laminae of the dorsal horn, the intermediate gray, and in lamina X surrounding the spinal canal. Within neurons, Dpp II was localized largely in cell perikarya and large primary dendrites with no staining observed in cell nuclei. Neurons in the superficial dorsal horn lack Dpp II enzyme activity. Nonneuronal elements which also stained prominently were pericytes associated with blood vessels and ependymal cells lining the lumen of the spinal canal. A few oligodendrocytes and astrocytes were also stained, but they represented a minor component of the total amount of Dpp II activity. Following ventral root injury, Dpp-II-containing motoneurons degenerate; some glial cells in the region of degenerating neurons become Dpp II positive. The localized distribution of Dpp II in spinal cord neurons suggests that this proteolytic enzyme may play a role in the metabolism of an unidentified neuropeptide.