Pain‐related reorganization in the primary somatosensory cortex of patients with postherpetic neuralgia

Studies on functional and structural changes in the primary somatosensory cortex (S1) have provided important insights into neural mechanisms underlying several chronic pain conditions. However, the role of S1 plasticity in postherpetic neuralgia (PHN) remains elusive. Combining psychophysics and magnetic resonance imaging (MRI), we investigated whether pain in PHN patients is linked to S1 reorganization as compared with healthy controls. Results from voxel‐based morphometry showed no structural differences between groups. To characterize functional plasticity, we compared S1 responses to noxious laser stimuli of a fixed intensity between both groups and assessed the relationship between S1 activation and spontaneous pain in PHN patients. Although the intensity of evoked pain was comparable in both groups, PHN patients exhibited greater activation in S1 ipsilateral to the stimulated hand. Pain‐related activity was identified in contralateral superior S1 (SS1) in controls as expected, but in bilateral inferior S1 (IS1) in PHN patients with no overlap between SS1 and IS1. Contralateral SS1 engaged during evoked pain in controls encoded spontaneous pain in patients, suggesting functional S1 reorganization in PHN. Resting‐state fMRI data showed decreased functional connectivity between left and right SS1 in PHN patients, which scaled with the intensity of spontaneous pain. Finally, multivariate pattern analyses (MVPA) demonstrated that BOLD activity and resting‐state functional connectivity of S1 predicted within‐subject variations of evoked and spontaneous pain intensities across groups. In summary, functional reorganization in S1 might play a key role in chronic pain related to PHN and could be a potential treatment target in this patient group.     

The role of the external lateral parabrachial subnucleus in flavor preferences induced by predigested food administered intragastrically

A study was undertaken of the role of the external lateral parabrachial subnucleus (PBNLe) in flavor preferences induced by the intragastric administration of predigested/cephalic food. These preferences were developed using two different learning procedures, concurrent and sequential. In the concurrent procedure, two different-flavored stimuli were presented at the same time: one stimulus was paired with the simultaneous intragastric administration of partially digested food and the other with physiological saline. In the sequential learning procedure, the two stimuli were presented at alternate sessions. The results showed that PBNLe lesions blocked acquisition of concurrent learning but had no effect on the sequential procedure. In the latter case, both lesioned and control animals showed a strong preference for the gustatory stimulus paired with partially digested food. These results are interpreted in terms of a dual neurobiological system involved in the rewarding effects of visceral signals.     

Neuropathic pain in spinal cord injury: significance of clinical and electrophysiological measures

A large percentage of spinal cord-injured subjects suffer from neuropathic pain below the level of the lesion (bNP). The neural mechanisms underlying this condition are not clear. The aim of this study was to elucidate the general effects of spinal deafferentiation and of bNP on electroencephalographic (EEG) activity. In addition, the relationship between the presence of bNP and impaired function of the spinothalamic tract was studied. Measurements were performed in complete and incomplete spinal cord-injured subjects with and without bNP as well as in a healthy control group. Spinothalamic tract function, assessed by contact heat evoked potentials, did not differ between subjects with and without bNP; nevertheless, it was impaired in 94% of subjects suffering from bNP. In the EEG recordings, the degree of deafferentiation was reflected in a slowing of EEG peak frequency in the 6–12-Hz band. Taking into account this unspecific effect, spinal cord-injured subjects with bNP showed significantly slower EEG activity than subjects without bNP. A discrimination analysis in the subjects with spinothalamic tract dysfunction correctly classified 84% of subjects as belonging to either the group with bNP or the group without bNP, according to their EEG peak frequency. These findings could be helpful for both the development of an objective diagnosis of bNP and for testing the effectiveness of new therapeutic agents.     

Sensory perception changes induced by transcranial magnetic stimulation over the primary somatosensory cortex in Parkinson's disease

Sensory symptoms are common nonmotor manifestations of Parkinson's disease. It has been hypothesized that abnormal central processing of sensory signals occurs in Parkinson's disease and is related to dopaminergic treatment. The objective of this study was to investigate the alterations in sensory perception induced by transcranial magnetic stimulation of the primary somatosensory cortex in patients with Parkinson's disease and the modulatory effects of dopaminergic treatment. Fourteen patients with Parkinson's disease with and without dopaminergic treatment and 13 control subjects were included. Twenty milliseconds after peripheral electrical tactile stimuli in the contralateral thumb, paired‐pulse transcranial magnetic stimulation over the right primary somatosensory cortex was delivered. We evaluated the perception of peripheral electrical tactile stimuli at 2 conditioning stimulus intensities, set at 70% and 90% of the right resting motor threshold, using different interstimulus intervals. At 70% of the resting motor threshold, paired‐pulse transcranial magnetic stimulation over the right primary somatosensory cortex induced an increase in positive responses at short interstimulus intervals (1–7 ms) in controls but not in patients with dopaminergic treatment. At 90% of the resting motor threshold, controls and patients showed similar transcranial magnetic stimulation effects. Changes in peripheral electrical tactile stimuli perception after paired‐pulse transcranial magnetic stimulation over the primary somatosensory cortex are altered in patients with Parkinson's disease with dopaminergic treatment compared with controls. These findings suggest that primary somatosensory cortex excitability could be involved in changes in somatosensory integration in Parkinson's disease with dopaminergic treatment. © 2011 Movement Disorder Society     

Upregulation of Group I metabotropic glutamate receptors in neurons and astrocytes in the dorsal horn following spinal cord injury

Of the glutamate receptor types, the metabotropic glutamate receptors (mGluRs) are G proteins coupled and can initiate a number of intracellular pathways leading to hyperexcitability of spinal neurons. In this study, we tested the expression of mGluRs to determine which cell types might contribute to sustained neuronal hyperexcitability in the lumbar enlargement with postoperative day (POD) 7 (early), 14 (late), and 30 (chronic phase) following spinal cord injury (SCI) by unilateral hemisection at T13 in Sprague-Dawley rats. Expression was determined by confocal analyses of immunocytochemical reaction product of neurons (NeuN positive) and astrocytes (GFAP positive) in the dorsal horn on both sides of the L4 segment. Neurons were divided into two sizes: small (<20 microm) and large (>35 microm), for physiological reasons. We report a significant increase of mGluR(1) expression in large and small neurons of the dorsal horn on both sides of the cord in late and chronic phases when compared to control sham groups. Expression of mGluR(2/3) significantly increased in large neurons on the ipsilateral (hemisected) side in the late phase. Expression of mGluR(5) significantly increased in large neurons in early, late, and chronic phases. In addition, mGluR(1) and mGluR(5) expression after hemisection was significantly increased in astrocytes in early, late, and chronic phases; whereas mGluR(2/3) did not display any significant changes. In conclusion, our data demonstrate long-term changes in expression levels of Group I mGluRs (mGluR(1) and mGluR(5)) in both neurons and astrocytes in segments below a unilateral SCI. Thus, permanent alterations in dorsal horn receptor expression may play important roles in transmission of nociceptive responses in the spinal cord following SCI.     

Remodeling of synaptic structures in the motor cortex following spinal cord injury

After spinal cord injury (SCI), structural reorganization occurs at multiple levels of the motor system including the motor cortex, and this remodeling may underlie recovery of motor function. The present study determined whether SCI leads to a remodeling of synaptic structures in the motor cortex. Dendritic spines in the rat motor cortex were visualized by confocal microscopy in fixed slices, and their density and morphology were analyzed after an overhemisection injury at C4 level. Spine density decreased at 7 days and partially recovered by 28 days. Spine head diameter significantly increased in a layer-specific manner. SCI led to a higher proportion of longer spines especially at 28 days, resulting in a roughly 10% increase in mean spine length. In addition, filopodium-like long dendritic protrusions were more frequently observed after SCI, suggesting an increase in synaptogenic events. This spine remodeling was accompanied by increased expression of polysialylated neural cell adhesion molecule, which attenuates adhesion between the pre- and postsynaptic membranes, in the motor cortex from as early as 3 days to 2 weeks after injury, suggesting a decrease in synaptic adhesion during the remodeling process. These results demonstrate time-dependent changes in spine density and morphology in the motor cortex following SCI. This synaptic remodeling seems to proceed with a time scale ranging from days to weeks. Elongation of dendritic spines may indicate a more immature and modifiable pattern of synaptic connectivity in the motor cortex being reorganized following SCI.     

Deposits of IgG and C3 in the spinal cord and motor cortex of ALS patients

Deposits of IgG and complement were demonstrated by direct immunofluorescent techniques with sections of motor cortex and spinal cord from amyotrophic lateral sclerosis (ALS) patients. Six of 16 ALS patients showed deposits within the spinal cord while 5 of 13 showed similar deposits within the motor cortex. The specificity of this staining was shown by blocking experiments and the use of conjugated F(ab')2. Similar deposits were found in the CNS in disease states associated with possible immune or infectious etiologies and were not found in the CNS of normal controls.     

Transplants of adrenal medullary chromaffin cells reduce forelimb and hindlimb allodynia in a rodent model of chronic central pain after spinal cord hemisection injury

In the majority of patients, spinal cord injury (SCI) results in abnormal pain syndromes in which non-noxious stimuli become noxious (allodynia). To reduce allodynia, it would be desirable to implant a permanent biological pump such as adrenal medullary chromaffin cells (AM), which secrete catecholamines and opioid peptides, both antinociceptive substances, near the spinal cord. We tested this approach using a recently developed a mammalian SCI model of chronic central pain, which results in development of mechanical and thermal allodynia. Thirty day-old male Sprague-Dawley rats were spinally hemisected at T13 and allowed 4 weeks for recovery of locomotor function and development of allodynia. Nonimmunosuppressed injured animals received either control-striated muscle (n = 7) or AM (n = 10) transplants. Nociceptive behavior was tested for 4 weeks posttransplant as measured by paw withdrawals to von Frey filaments, radiant heat, and pin prick stimuli. Hemisected animals receiving AM demonstrated statistically significant reductions in both fore- and hindlimb mechanical and thermal allodynia, but not analgesia, when compared to hemisected animals receiving striated muscle transplants (P < 0.05). Tyrosine hydroxylase immunoreactivity indicated prolonged transplant survival and production of catecholamines. HPLC analysis of cerebrospinal fluid samples from animals receiving AM transplants demonstrated statistically significant increases in levels of dopamine (sevenfold), norepinephrine (twofold), and epinephrine (threefold), compared to control values several weeks following transplant (P < 0.05). By 28 days posttransplant, however, antinociceptive effects were diminished. These results support the therapeutic potential of transplanted AM in reducing chronic central pain following spinal cord injury.     

Neuropathology of the intermediolateral nucleus of the spinal cord in sudden unexplained perinatal and infant death

Experimental studies have demonstrated that breathing activity in rats is generated early in embryonic stages in rostral spinal cord, precisely in the intermediolateral nucleus, then establishing a spinal cord–brainstem network.     

Plasticity changes of neuronal activities in central lateral nucleus by stimulation of the anterior cingulate cortex in rat

The medial thalamus (MT) and anterior cingulate cortex (ACC) are essential components in mediating the affective emotional-aspect of pain. Whether ACC modulates the neuron activity in MT has not been elucidated and clarifying this point will further reveal the neurobiological mechanism underlying pain related emotions. In the present study, we used in vivo single unit recording and retrograde tracing technique to demonstrate that the majority of examined neurons in the central lateral nucleus (CL), an important nucleus of MT, responded to noxious stimulation. Tetanic stimulation in the ACC increased spike activities of nociceptive-responding neurons in the CL; retrograde tracing by fluorogold in the CL showed the positive neurons are distributed bilaterally in the ACC. Taken together, we demonstrated descending modulation to nociceptive responses of CL neurons by direct projections from the ACC, which may underlie the neuronal mechanism of negative pain emotions.     

Sodium deprivation and salt intake activate separate neuronal subpopulations in the nucleus of the solitary tract and the parabrachial complex

Salt intake is an established response to sodium deficiency, but the brain circuits that regulate this behavior remain poorly understood. We studied the activation of neurons in the nucleus of the solitary tract (NTS) and their efferent target nuclei in the pontine parabrachial complex (PB) in rats during sodium deprivation and after salt intake. After 8-day dietary sodium deprivation, immunoreactivity for c-Fos (a neuronal activity marker) increased markedly within the aldosterone-sensitive neurons of the NTS, which express the enzyme 11-beta-hydroxysteroid dehydrogenase type 2 (HSD2). In the PB, c-Fos labeling increased specifically within two sites that relay signals from the HSD2 neurons to the forebrain--the pre-locus coeruleus and the innermost region of the external lateral parabrachial nucleus. Then, 1-2 hours after sodium-deprived rats ingested salt (a hypertonic 3% solution of NaCl), c-Fos immunoreactivity within the HSD2 neurons was virtually eliminated, despite a large increase in c-Fos activation in the surrounding NTS (including the A2 noradrenergic neurons) and area postrema. Also after salt intake, c-Fos activation increased within pontine nuclei that relay gustatory (caudal medial PB) and viscerosensory (rostral lateral PB) information from the NTS to the forebrain. Thus, sodium deficiency and salt intake stimulate separate subpopulations of neurons in the NTS, which then transmit this information to the forebrain via largely separate relay nuclei in the PB complex. These findings offer new perspectives on the roles of sensory information from the brainstem in the regulation of sodium appetite.     

Long‐term neuroplasticity of the face primary motor cortex and adjacent somatosensory cortex induced by tooth loss can be reversed following dental implant replacement in rats

Tooth loss is common, and exploring the neuroplastic capacity of the face primary motor cortex (face‐M1) and adjacent primary somatosensory cortex (face‐S1) is crucial for understanding how subjects adapt to tooth loss and their prosthetic replacement. The aim was to test if functional reorganization of jaw and tongue motor representations in the rat face‐M1 and face‐S1 occurs following tooth extraction, and if subsequent dental implant placement can reverse this neuroplasticity. Rats (n = 22) had the right maxillary molar teeth extracted under local and general anesthesia. One month later, seven rats had dental implant placement into healed extraction sites. Naive rats (n = 8) received no surgical treatment. Intracortical microstimulation (ICMS) and recording of evoked jaw and tongue electromyographic responses were used to define jaw and tongue motor representations at 1 month (n = 8) or 2 months (n = 7) postextraction, 1 month postimplant placement, and at 1–2 months in naive rats. There were no significant differences across study groups in the onset latencies of the ICMS‐evoked responses (P > 0.05), but in comparison with naive rats, tooth extraction caused a significant (P < 0.05) and sustained (1–2 months) decreased number of ICMS‐defined jaw and tongue sites within face‐M1 and ‐S1, and increased thresholds of ICMS‐evoked responses in these sites. Furthermore, dental implant placement reversed the extraction‐induced changes in face‐S1, and in face‐M1 the number of jaw sites even increased as compared to naive rats. These novel findings suggest that face‐M1 and adjacent face‐S1 may play a role in adaptive mechanisms related to tooth loss and their replacement with dental implants. J. Comp. Neurol. 523:2372–2389, 2015. © 2015 Wiley Periodicals, Inc.     

Effects of serotonin inhibition on neuronal and astrocyte plasticity in the phrenic nucleus 4 h following C2 spinal cord hemisection

C2 spinal cord hemisection results in synaptic and astroglial changes in the phrenic nucleus which have been associated with the recovery of the ipsilateral hemidiaphragm during expression of the crossed phrenic phenomenon. As part of our ongoing analysis of the neurotransmitters involved, the present study investigated the effects of systemic administration of para-chlorophenylalanine (p-CPA), a serotonin (5-HT) synthesis inhibitor, on plasticity in the rat phrenic nucleus 4 h following C2 hemisection. Hemisected control rats demonstrated typical morphological changes in the ipsilateral phrenic nucleus including: (1) an increased number and length of synaptic active zones and (2) an increased number and length of dendrodendritic membrane appositions. p-CPA treatment 3 days prior to hemisection reduced 5-HT levels and resulted in an attenuation of these changes in the ipsilateral phrenic nucleus 4 h following hemisection compared to hemisected controls. In addition, p-CPA treatment attenuated injury-induced alterations in immunohistochemical staining of glial fibrillary acidic protein (GFAP), although Western blot analysis demonstrated that overall levels of GFAP did not differ significantly between groups. The results suggest that inhibition of 5-HT synthesis by p-CPA attenuates hemisection-induced plasticity in the phrenic nucleus 4 h following an ipsilateral C2 hemisection.     

Adaptive changes in the neuromagnetic response of the primary and association somatosensory areas following repetitive tactile hand stimulation in humans

Cortical adaptation in the primary somatosensory cortex (SI) has been probed using different stimulation modalities and recording techniques, in both human and animal studies. In contrast, considerably less knowledge has been gained about the adaptation profiles in other areas of the cortical somatosensory network. Using magnetoencephalography (MEG), we examined the patterns of short‐term adaptation for evoked responses in SI and somatosensory association areas during tactile stimulation applied to the glabrous skin of the hand. Cutaneous stimuli were delivered as trains of serial pulses with a constant frequency of 2 Hz and 4 Hz in separate runs, and a constant inter‐train interval of 5 s. The unilateral stimuli elicited transient responses to the serial pulses in the train, with several response components that were separated by independent component analysis. Subsequent source reconstruction techniques identified regional generators in the contralateral SI and somatosensory association areas in the posterior parietal cortex (PPC). Activity in the bilateral secondary somatosensory cortex (i.e., SII/PV) was also identified, although less consistently across subjects. The dynamics of the evoked activity in each area and the frequency‐dependent adaptation effects were assessed from the changes in the relative amplitude of serial responses in each train. We show that the adaptation profiles in SI and PPC areas can be quantitatively characterized from neuromagnetic recordings using tactile stimulation, with the sensitivity to repetitive stimulation increasing from SI to PPC. A similar approach for SII/PV has proven less straightforward, potentially due to the tendency of these areas to respond selectively to certain stimuli. Hum Brain Mapp, 2013. © 2012 Wiley Perodicals, Inc.     

Comparison of the spinal neuropathic pain induced by intraspinal injection of N-methyl-d-aspartate and quisquate in rats

Objective

Excitatory amino acids play important roles in the development of secondary pathology following spinal cord injury (SCI). This study was designed to evaluate morphological changes in the dorsal horn of the spinal cord and assess profiles of pain behaviors following intraspinal injection of N-methyl-D-aspartate (NMDA) or quisqualate (QUIS) in rats.

Methods

Forty male Sprague-Dawley rats were randomized into three groups : a sham, and two experimental groups receiving injections of 125 mM NMDA or QUIS into their spinal dorsal horn. Following injection, hypersensitivity to cold and mechanical stimuli, and excessive grooming behaviors were assessed serially for four weeks. At the end of survival periods, morphological changes in the spinal cord were evaluated.

Results

Cold allodynia was developed in both the NMDA and QUIS groups, which was significantly higher in the QUIS group than in the NMDA group. The mechanical threshold for the ipsilateral hind paw in both QUIS and NMDA groups was significantly lower than that in the control group. The number of groomers was significantly higher in the NMDA group than in the QUIS group. The size of the neck region of the spinal dorsal horn, but not the superficial layer, was significantly smaller in the NMDA and QUIS groups than in the control group.

Conclusion

Intraspinal injection of NMDA or QUIS can be used as an excitotoxic model of SCI for further research on spinal neuropathic pain.     

Structural development of the lateral geniculate nucleus and visual cortex in monkey and man

This study concerns the development of the primary visual pathway of the primate. The lateral geniculate nucleus (LGN) is the principal thalamic relay to the visual cortex (area 17), and its neurons have similar morphological characteristics in both monkey and man, as identified by Golgi impregnation. The commonest neuron is the multipolar with a radiate or tufted dendritic tree; next is the bipolar neuron with two or three diametrically opposed dendritic trunks. Less frequent are neurons with beaded dendrites and others with fine, axon-like dendritic processes, possibly interneurons. The dendritic tree of all neurons remains generally within a lamina, but some dendrites cross interlaminar zones. LGN neurons are identifiable before birth and differ from their adult form by the presence of immature features, especially numerous dendritic and somatic spines, most frequent at birth in monkeys and at about 4 months postnatally in man. They disappear almost completely by 3 months in monkeys and 9 months in man. The human LGN has reached its ‘adult’ volume by this age.Two stages in the development of the human area 17 can be defined. The first is marked by a rapid growth to its ‘adult’ volume by about 4 months, and by intense synaptogenesis beginning in the foetus and reaching a maximum around 8 months. The second stage is one of stabilization in the volume of area 17 and loss of synapses to reach ‘adult’ synaptic density around 11 years, at about 60% of the maximum values.The formation of transitory morphological features in the first weeks or months of life coincides with a period of visual plasticity in infant monkeys and humans. Our observations can be correlated with experimental evidence for visual development in monkeys and with clinical evaluation of visual activity during the human preverbal stage, a period of great importance in the establishment of visual acuity, of stereopsis and of oculomotor function, all very sensitive to the numerous forms of visual deprivation.     

The primary somatosensory cortex and the insula contribute differently to the processing of transient and sustained nociceptive and non‐nociceptive somatosensory inputs

Transient nociceptive stimuli elicit consistent brain responses in the primary and secondary somatosensory cortices (S1, S2), the insula and the anterior and mid‐cingulate cortex (ACC/MCC). However, the functional significance of these responses, especially their relationship with sustained pain perception, remains largely unknown. Here, using functional magnetic resonance imaging, we characterize the differential involvement of these brain regions in the processing of sustained nociceptive and non‐nociceptive somatosensory input. By comparing the spatial patterns of activity elicited by transient (0.5 ms) and long‐lasting (15 and 30 s) stimuli selectively activating nociceptive or non‐nociceptive afferents, we found that the contralateral S1 responded more strongly to the onset of non‐nociceptive stimulation as compared to the onset of nociceptive stimulation and the sustained phases of nociceptive and non‐nociceptive stimulation. Similarly, the anterior insula responded more strongly to the onset of nociceptive stimulation as compared to the onset of non‐nociceptive stimulation and the sustained phases of nociceptive and non‐nociceptive stimulation. This suggests that S1 is specifically sensitive to changes in incoming non‐nociceptive input, whereas the anterior insula is specifically sensitive to changes in incoming nociceptive input. Second, we found that the MCC responded more strongly to the onsets as compared to the sustained phases of both nociceptive and non‐nociceptive stimulation, suggesting that it could be involved in the detection of change regardless of sensory modality. Finally, the posterior insula and S2 responded maximally during the sustained phase of non‐nociceptive stimulation but not nociceptive stimulation, suggesting that these regions are preferentially involved in processing non‐nociceptive somatosensory input. Hum Brain Mapp 36:4346–4360, 2015. © 2015 Wiley Periodicals, Inc.     

Therapeutic potential of progesterone in spinal cord injury-induced neuropathic pain: At the crossroads between neuroinflammation and N-methyl-D-aspartate receptor

In recent decades, an area of active research has supported the notion that progesterone promotes a wide range of remarkable protective actions in experimental models of nervous system trauma or disease, and has also provided a strong basis for considering this steroid as a promising molecule for modulating the complex maladaptive changes that lead to neuropathic pain, especially after spinal cord injury. In this review, we intend to give the readers a brief appraisal of the main mechanisms underlying the increased excitability of the spinal circuit in the pain pathway after trauma, with particular emphasis on those mediated by the activation of resident glial cells, the subsequent release of proinflammatory cytokines and their impact on N-methyl-D-aspartate receptor function. We then summarize the available preclinical data pointing to progesterone as a valuable repurposing molecule for blocking critical cellular and molecular events that occur in the dorsal horn of the injured spinal cord and are related to the development of chronic pain. Since the treatment and management of neuropathic pain after spinal injury remains challenging, the potential therapeutic value of progesterone opens new traslational perspectives to prevent central pain.     

Effects of T2 spinal transection on compensation of horizontal canal related activity in the medial vestibular nucleus following unilateral labyrinth ablation in the decerebrate gerbil

The effects of spinal transection at T₂ upon static and dynamic responses of type I and II neurons in the medial vestibular nucleus after vestibular compensation were investigated in decerebrate Mongolian gerbils (Meriones unguiculatus). Spinal transection in compensated animals resulted in bilaterally depressed spontaneous activity and asymmetry in the response gain of type I neurons, suggesting that tonic spinal inputs contribute to vestibular compensation through effects upon type I neurons.     

Loss and spontaneous recovery of forelimb evoked potentials in both the adult rat cuneate nucleus and somatosensory cortex following contusive cervical spinal cord injury

Varying degrees of neurologic function spontaneously recovers in humans and animals during the days and months after spinal cord injury (SCI). For example, abolished upper limb somatosensory potentials (SSEPs) and cutaneous sensations can recover in persons post-contusive cervical SCI. To maximize recovery and the development/evaluation of repair strategies, a better understanding of the anatomical locations and physiological processes underlying spontaneous recovery after SCI is needed. As an initial step, the present study examined whether recovery of upper limb SSEPs after contusive cervical SCI was due to the integrity of some spared dorsal column primary afferents that terminate within the cuneate nucleus and not one of several alternate routes. C5-6 contusions were performed on male adult rats. Electrophysiological techniques were used in the same rat to determine forelimb evoked neuronal responses in both cortex (SSEPs) and the cuneate nucleus (terminal extracellular recordings). SSEPs were not evoked 2 days post-SCI but were found at 7 days and beyond, with an observed change in latencies between 7 and 14 days (suggestive of spared axon remyelination). Forelimb evoked activity in the cuneate nucleus at 15 but not 3 days post-injury occurred despite dorsal column damage throughout the cervical injury (as seen histologically). Neuroanatomical tracing (using 1% unconjugated cholera toxin B subunit) confirmed that upper limb primary afferent terminals remained within the cuneate nuclei. Taken together, these results indicate that neural transmission between dorsal column primary afferents and cuneate nuclei neurons is likely involved in the recovery of upper limb SSEPs after contusive cervical SCI.