scholarly journals Effects of a Cannabinoid Agonist on Spinal Nociceptive Neurons in a Rodent Model of Neuropathic Pain

2006 ◽  
Vol 96 (6) ◽  
pp. 2984-2994 ◽  
Author(s):  
Cheng Liu ◽  
J. Michael Walker
Keyword(s):  
Neuropathic Pain ◽  
Receptive Field ◽  
Nerve Injury ◽  
Dynamic Range ◽  
Rodent Model ◽  
Field Size ◽  
Neural Basis ◽  
Noxious Heat ◽  
Nociceptive Neurons ◽  
Wdr Neurons

The effects of the synthetic cannabinoid WIN 55,212–2 on heat-evoked firing of spinal wide dynamic range (WDR) neurons were examined in a rodent model of neuropathic pain. Fifty-eight WDR neurons (1 cell/animal) were recorded from the ipsilateral spinal dorsal horns of rats with chronic constriction injury (CCI) and sham-operated controls. Relative to sham-operated controls, neurons recorded in CCI rats showed elevations in spontaneous firing, noxious heat-evoked responses, and afterdischarge firing as well as increases in receptive field size. WIN 55,212–2 (0.0625, 0.125, and 0.25 mg/kg, intravenous) dose-dependently suppressed heat-evoked activity and decreased the receptive field areas of dorsal horn WDR neurons in both nerve injured and control rats with a greater inhibition in CCI rats. At the dose of 0.125 mg/kg iv, WIN 55,212–2 reversed the hyperalgesia produced by nerve injury. The effect of intravenous administration of WIN 55,212–2 appears to be centrally mediated because administration of the drug directly to the ligated nerve did not suppress the heat-evoked neuronal activity in CCI rats. Pretreatment with the cannabinoid CB1 receptor antagonists SR141716A or AM251, but not the CB2 antagonist SR144528, blocked the effects. These results provide a neural basis for reports of potent suppression by cannabinoids of the abnormal sensory responses that result from nerve injury.

Responses of monkey medullary dorsal horn neurons during the detection of noxious heat stimuli

1989 ◽  
Vol 62 (2) ◽  
pp. 437-449 ◽  
Author(s):  
W. Maixner ◽  
R. Dubner ◽  
D. R. Kenshalo ◽  
M. C. Bushnell ◽  
J. L. Oliveras
Keyword(s):  
Dorsal Horn ◽  
Stimulus Intensity ◽  
Dynamic Range ◽  
Thermal Stimulus ◽  
Mechanical Stimuli ◽  
Behavioral Task ◽  
Noxious Heat ◽  
Nociceptive Neurons ◽  
Medullary Dorsal Horn ◽  
Wdr Neurons

1. We examined the activity of thermally sensitive trigeminothalamic neurons and nonprojection neurons in the medullary dorsal horn (trigeminal nucleus caudalis) in three monkeys performing thermal and visual detection tasks. 2. An examination of neuronal stimulus-response functions, obtained during thermal-detection tasks in which noxious heat stimuli were applied to the face, indicated that wide-dynamic-range neurons (WDR, responsive to innocuous mechanical stimuli with greater responses to noxious mechanical stimuli) could be subclassified based on the slope values of linear regression lines. WDR1 neurons exhibited significantly greater sensitivity to noxious heat stimulation than WDR2 neurons or nociceptive-specific neurons (NS, responsive only to noxious stimuli). 3. In one behavioral task, the monkeys detected 1.0 degrees C increases in noxious heat from preceding noxious heat stimuli ranging from 44 to 48 degrees C. WDR1, WDR2, and NS neurons increased their discharge frequency as a function of the intensity of the first noxious heat temperature (T1) as well as the final temperature (T2). The responses of WDR1 neurons were greater than those produced by WDR2 or NS neurons across all the temperatures examined. The order of stimulus presentation affected the responses of WDR1 neurons to 1.0 degrees C increases in the noxious heat range but not those of WDR2 or NS neurons. 4. In a second behavioral task, the monkeys detected small increases in noxious heat (0.2-0.8 degrees C) from a first temperature of 46 degrees C. Although the responses of all three classes of neurons were monotonically related to stimulus intensity, WDR1 neurons exhibited greater sensitivity to small temperature increases than either WDR2 or NS neurons. 5. Subpopulations of all three classes of neurons exhibited responses that were independent of thermal stimulus parameters or sensory modality and that only occurred during the behavioral task. These task-related responses were time-locked to specific behavioral events associated with trial initiation and trial continuation. 6. These data provide evidence that a subpopulation of WDR neurons is the dorsal horn cell type most sensitive to small increases in noxious heat in the 45-49 degrees C temperature range and provides the most information about stimulus intensity. The findings support the view that nociceptive neurons have the capacity to precisely encode stimulus features in the noxious range and that WDR neurons are likely to participate in the monkeys' ability to perceive the intensity of such stimuli.

scholarly journals The Antiallodynic Action of Pregabalin May Depend on the Suppression of Spinal Neuronal Hyperexcitability in Rats with Spared Nerve Injury

2014 ◽  
Vol 19 (4) ◽  
pp. 205-211 ◽  
Author(s):  
Lei Ding ◽  
Jie Cai ◽  
Xiang-Yang Guo ◽  
Xiu-Li Meng ◽  
Guo-Gang Xing
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Horn ◽  
Nerve Injury ◽  
Dynamic Range ◽  
Inhibitory Effect ◽  
Electrophysiological Recording ◽  
Spared Nerve Injury ◽  
Withdrawal Threshold ◽  
Wdr Neurons

BACKGROUND: Pregabalin (PGB) is a novel antiepileptic drug and is also used as a first-line medication for the treatment of neuropathic pain. However, the mechanisms of its analgesic effects remain largely unknown.OBJECTIVES: To elucidate the mechanisms underlying the antiallodynic action of PGB in rats with neuropathic pain.METHODS: In a rat model of neuropathic pain induced by spared nerve injury, mechanical allodynia, as a behavioural sign of neuropathic pain, was assessed by measuring 50% paw withdrawal threshold with von Frey filaments. Activities of dorsal horn wide dynamic range (WDR) neurons were examined by extracellular electrophysiological recording in vivo.RESULTS: Spinal administration of PGB exerted a significant antiallodynic effect and a prominent inhibitory effect on the hypersensitivity of dorsal horn WDR neurons in rats with spared nerve injury.CONCLUSION: The antiallodynic action of PGB is likely dependent on the suppression of WDR neuron hyperexcitability in rats with neuropathic pain.

Nociceptive neurons in rat superior colliculus: response properties, topography, and functional implications

1989 ◽  
Vol 62 (2) ◽  
pp. 510-525 ◽  
Author(s):  
J. G. McHaffie ◽  
C. Q. Kao ◽  
B. E. Stein
Keyword(s):  
Superior Colliculus ◽  
Dynamic Range ◽  
The Body ◽  
Body Parts ◽  
Power Functions ◽  
Noxious Heat ◽  
Nociceptive Neurons ◽  
Tactile Stimuli ◽  
Noxious Stimuli ◽  
Wdr Neurons

1. Extracellular recordings were made from single superior colliculus neurons in urethane-anesthetized rats in response to mechanical and/or thermal stimulation of the skin. In addition to those activated by low-threshold (LT) tactile stimuli, many neurons responded preferentially, or solely, to noxious stimuli. Two functionally defined subtypes of nociceptive neurons were distinguished: wide-dynamic-range (WDR) neurons, which responded optimally to noxious stimuli but also to innocuous stimuli; and nociceptive-specific (NS) neurons, which responded solely to frankly noxious stimuli. The thermal thresholds were 42-45 degrees C, and the stimulus-response relationships were positively accelerating power functions with exponents of 2.9 (WDR) and 3.1 (NS). 2. WDR neurons also responded to cooling of the skin to temperatures below 24 degrees C. Like noxious heat responses, cold responses were monotonically graded as the intensity of the cold stimulus was increased. Thus the temperature sensitivity of thermal-sensitive neurons in the superior colliculus appeared to be tuned to detect large deviations from ambient skin temperature in either direction once threshold is reached. 3. LT neurons were somatotopically organized, with the head and forelimbs rostral and the trunk and hindlimbs caudal. The limbs were generally represented further lateral in the structure, whereas more proximal body parts were more medial. Nevertheless, there was extensive overlap of body parts especially in areas of transition. Thus, a "block-to-block" or "area-to-area" rather than a "point-to-point" representation of the body surface was evident. 4. The nociceptive representation did not violate the general LT somatotopy but neither was it coextensive. Virtually all nociceptive neurons had trigeminal receptive fields and were thus heavily represented in the rostral superior colliculus, where the LT face representation was also located. No nociceptive neurons were present in the caudal one-third of the structure. A general dorsal-to-ventral segregation of somatosensory neurons also was noted, so that in a given electrode penetration, LT neurons usually were the most superficial, WDR neurons were just below these, and NS neurons were deepest of all. 5. The presence of overlapping LT and nociceptive trigeminal representations in the superior colliculus seems particularly adaptive in view of the fact that rodents use their vibrissae for exploring their environment and thus put rostral body parts at risk during such behaviors.(ABSTRACT TRUNCATED AT 400 WORDS)

Investigating mechanisms behind offset analgesia: Effect on spinal responses during thermal stimulation

2014 ◽  
Vol 5 (3) ◽  
pp. 207-208
Author(s):  
Thomas Kronborg Larsen ◽  
Andreas Egmose ◽  
Marianne Enggaard ◽  
Rósa Hugosdóttir ◽  
Federico Arguissain ◽  
...  
Keyword(s):  
Dynamic Range ◽  
Tibialis Anterior Muscle ◽  
Noxious Heat ◽  
Baseline Trial ◽  
Nociceptive Neurons ◽  
Pain Ratings ◽  
Subjective Pain ◽  
Wdr Neurons ◽  
Perceptual Mechanism ◽  
Stimulation Of

AbstractIntroductionOffset analgesia (OA) is a temporal perceptual mechanism in which subjective pain ratings decrease disproportionally when a noxious heat stimulus is decreased by 1–3 ◦C. Whether OA is a peripheral, spinal or supraspinal mechanism remains unknown. The stimulation of afferent nociceptors in the foot, leads to a spinal nociceptive withdrawal reflex (NWR) which is mediated through the wide dynamic range (WDR) neurons and therefore under descending control. We hypothesized that OA affects the spinal nociceptive neurons resulting in an attenuation of the NWR during OA.MethodsFour heat stimulations profiles were applied to the lower legs divided into four segments of 5 s, 5 s, 5 s, and 15 s, respectively: Offset Analgesia Trial (OAT) (48, 49, 48, 48 ◦C), Offset Baseline Trial (OBT) (48, 49, 32, 32 ◦C), Constant Heat Trial (CHT) (4 × 48 ◦C), and Baseline Trial (BT) (4 × 32 ◦C). Subjects rated the pain intensity continuously using a visual analog scale (VAS). NWR were evoked by electrical stimulation of the plantar foot and assessed once during each segment by recording EMG from the tibialis anterior muscle.ResultsVAS-ratings were lower during the third period of OAT compared to CHT (p < 0.001). However, there was no difference (p > 0.05) comparing the NWR size between OAT, OBT, CHT, and BT throughout the time periods.ConclusionsThe NWR was not affected by OA suggesting that spinal WDR plays a limited role in the OA mechanism. Whether peripheral- or supraspinal mechanisms are responsible the OA phenomenon remains unknown.

Cannabinoid Suppression of Noxious Heat-Evoked Activity in Wide Dynamic Range Neurons in the Lumbar Dorsal Horn of the Rat

1999 ◽  
Vol 81 (2) ◽  
pp. 575-583 ◽  
Author(s):  
Andrea G. Hohmann ◽  
Kang Tsou ◽  
J. Michael Walker
Keyword(s):  
Dorsal Horn ◽  
Dynamic Range ◽  
Cb1 Receptors ◽  
Intraventricular Administration ◽  
Wide Dynamic Range ◽  
Noxious Heat ◽  
Nociceptive Neurons ◽  
Evoked Activity ◽  
Wdr Neurons ◽  
Wide Dynamic Range Neurons

Cannabinoid suppression of noxious heat-evoked activity in wide dynamic range neurons in the lumbar dorsal horn of the rat. The effects of cannabinoid agonists on noxious heat-evoked firing of 62 spinal wide dynamic range (WDR) neurons were examined in urethan-anesthetized rats (1 cell/animal). Noxious thermal stimulation was applied with a Peltier device to the receptive fields in the ipsilateral hindpaw of isolated WDR neurons. To assess the site of action, cannabinoids were administered systemically in intact and spinally transected rats and intraventricularly. Both the aminoalkylindole cannabinoid WIN55,212-2 (125 μg/kg iv) and the bicyclic cannabinoid CP55,940 (125 μg/kg iv) suppressed noxious heat-evoked activity. Responses evoked by mild pressure in nonnociceptive neurons were not altered by CP55,940 (125 μg/kg iv), consistent with previous observations with another cannabinoid agonist, WIN55,212-2. The cannabinoid induced-suppression of noxious heat-evoked activity was blocked by pretreatment with SR141716A (1 mg/kg iv), a competitive antagonist for central cannabinoid CB1 receptors. By contrast, intravenous administration of either vehicle or the receptor-inactive enantiomer WIN55,212-3 (125 μg/kg) failed to alter noxious heat-evoked activity. The suppression of noxious heat-evoked activity induced by WIN55,212-2 in the lumbar dorsal horn of intact animals was markedly attenuated in spinal rats. Moreover, intraventricular administration of WIN55,212-2 suppressed noxious heat-evoked activity in spinal WDR neurons. By contrast, both vehicle and enantiomer were inactive. These findings suggest that cannabinoids selectively modulate the activity of nociceptive neurons in the spinal dorsal horn by actions at CB1 receptors. This modulation represents a suppression of pain neurotransmission because the inhibitory effects are selective for pain-sensitive neurons and are observed with different modalities of noxious stimulation. The data also provide converging lines of evidence for a role for descending antinociceptive mechanisms in cannabinoid modulation of spinal nociceptive processing.

Somatotopic distribution of trigeminal nociceptive neurons in ventrobasal complex of cat thalamus

1985 ◽  
Vol 53 (6) ◽  
pp. 1387-1400 ◽  
Author(s):  
T. Yokota ◽  
N. Koyama ◽  
N. Matsumoto
Keyword(s):  
Receptive Field ◽  
Dynamic Range ◽  
Tooth Pulp ◽  
Mechanical Stimuli ◽  
Canine Tooth ◽  
Light Pressure ◽  
Nociceptive Neurons ◽  
Low Threshold ◽  
Rostral Part ◽  
Shell Region

Recordings were made from single thalamic units in the urethan-chloralose anesthetized cat. Altogether 2,905 trigeminal single units having a receptive field in the contralateral trigeminal integument were isolated from the somatosensory part of nucleus ventralis posteromedialis, or VPM proper. Each isolated unit was tested for responses to a series of mechanical stimuli. The stimuli included brushing the skin, touch, pressure, noxious pinch, and pinpricks. The majority of VPM proper units responded with the greatest discharge frequency to gentle mechanical stimulation: either hair movement or light pressure to the trigeminal integument, but 341 units were identified as trigeminal nociceptive units. They were partitioned into two functionally defined subclasses, nociceptive specific (NS) and wide dynamic range (WDR) units, but not intermingled with low-threshold mechanoreceptive (LTM) units. Both NS and WDR units were found at or near the margin of the VPM proper but not outside this nucleus. This marginal area was referred to as the shell region of the VPM proper. A total of 248 NS units was found within the shell region of the caudal third of the VPM proper. This part was called the NS zone. These units were somatotopically organized. In the rostral part of the NS zone, ophthalmic NS units having a receptive field in the contralateral ophthalmic division were located dorsolaterally, maxillary NS units occurred dorsomedially, and mandibular NS units were found ventromedially. In the caudal part of the NS zone, maxillary NS units were encountered in the dorsal shell region, whereas mandibular NS units were found in the ventromedial shell region. Ophthalmic NS units were not found in this part of the NS zone. Altogether 93 WDR units were encountered in the shell region of the VPM proper. They were confined to a narrow band approximately 300 micron wide just rostral to the NS zone. These units were somatotopically organized. Ophthalmic WDR units having a low-threshold center of the receptive field in the contralateral ophthalmic division were located dorsolaterally, maxillary WDR units were located dorsomedially, and mandibular WDR units were located ventromedially. The majority of maxillary as well as mandibular WDR units were activated by electrical stimulation of the contralateral maxillary and/or mandibular canine tooth pulp afferents. Both NS and WDR zones of the VPM proper extended into the shell region of the nucleus ventralis posterolateralis (VPL).(ABSTRACT TRUNCATED AT 400 WORDS)

Responses of primate SI cortical neurons to noxious stimuli

1983 ◽  
Vol 50 (6) ◽  
pp. 1479-1496 ◽  
Author(s):  
D. R. Kenshalo ◽  
O. Isensee
Keyword(s):  
Receptive Field ◽  
Cortical Neurons ◽  
Receptive Fields ◽  
The Body ◽  
Thermal Stimulation ◽  
Discharge Frequency ◽  
Mechanical Stimuli ◽  
Noxious Heat ◽  
Nociceptive Neurons ◽  
Heat Pulses

Recordings were made from single SI cortical neurons in the anesthetized macaque monkey. Each isolated cortical neuron was tested for responses to a standard series of mechanical stimuli. The stimuli included brushing the skin, pressure, and pinch. The majority of cortical neurons responded with the greatest discharge frequency to brushing the receptive field, but neurons were found in areas 3b and 1 that responded maximally to pinching the receptive field. A total of 68 cortical nociceptive neurons were examined in 10 animals. Cortical neurons that responded maximally to pinching the skin were also tested for responses to graded noxious heat pulses (from 35 to 43, 45, 47, and 50 degrees C). If the neuron failed to respond or only responded to 50 degrees C, the receptive field was also heated to temperatures of 53 and 55 degrees C. Fifty-six of the total population of nociceptive neurons were tested for responses to the complete series of noxious heat pulses: 46 (80%) exhibited a progressive increase in the discharge frequency as a function of stimulus intensity, and the spontaneous activity of two (4%) was inhibited. One population of cortical nociceptive neurons possessed restricted, contralateral receptive fields. These cells encoded the intensity of noxious mechanical and thermal stimulation. Sensitization of primary afferent nociceptors was reflected in the responses of SI cortical nociceptive neurons when the ascending series of noxious thermal stimulation was repeated. The population of cortical nociceptive neurons with restricted receptive fields exhibited no adaptation in the response during noxious heat pulses of 47 and 50 degrees C. At higher temperatures the response often continued to increase during the stimulus. The other population of cortical nociceptive neurons was found to have restricted, low-threshold receptive fields on the contralateral hindlimb and, in addition, could be activated only by intense pinching or noxious thermal stimuli delivered on any portion of the body. The stimulus-response functions obtained from noxious thermal stimulation of the contralateral hindlimb were not different from cortical nociceptive neurons with small receptive fields. However, nociceptive neurons with large receptive fields exhibited a consistent adaptation during a noxious heat pulse of 47 and 50 degrees C. Based on the response characteristics of these two populations of cortical nociceptive neurons, we conclude that neurons with small receptive fields possess the ability to provide information about the localization, the intensity, and the temporal attributes of a noxious stimulus.4+.

α2-Adrenoceptors Modulate NMDA-Evoked Responses of Neurons in Superficial and Deeper Dorsal Horn of the Medulla

1998 ◽  
Vol 80 (4) ◽  
pp. 2210-2214 ◽  
Author(s):  
Kai-Ming Zhang ◽  
Xiao-Min Wang ◽  
Angela M. Peterson ◽  
Wen-Yan Chen ◽  
Sukhbir S. Mokha
Keyword(s):  
Dorsal Horn ◽  
Dynamic Range ◽  
Inhibitory Effect ◽  
Male Rats ◽  
Evoked Responses ◽  
Superficial Dorsal Horn ◽  
Nociceptive Neurons ◽  
Adrenoceptor Antagonist ◽  
Medullary Dorsal Horn ◽  
Wdr Neurons

Kai-Ming Zhang, Xiao-Min Wang, Angela M. Peterson, Wen-Yan Chen, and Sukhbir S. Mokha. α2-Adrenoceptors modulate NMDA-evoked responses of neurons in the superficial and deeper dorsal horn of the medulla. J. Neurophysiol. 80: 2210–2214, 1998. Extracellular single unit recordings were made from neurons in the superficial and deeper dorsal horn of the medulla (trigeminal nucleus caudalis) in 21 male rats anesthetized with urethan. NMDA produced an antagonist-reversible excitation of 46 nociceptive as well as nonnociceptive neurons. Microiontophoretic application of a preferential α2-adrenoceptor (α2AR) agonist, (2-[2,6-dichloroaniline]-2-imidazoline) hydrochloride (clonidine), reduced the NMDA-evoked responses of 86% (6/7) of nociceptive-specific (NS) neurons, 82% (9/11) of wide dynamic range (WDR) neurons, and 67% (4/6) of low-threshold (LT) neurons in the superficial dorsal horn. In the deeper dorsal horn, clonidine inhibited the NMDA-evoked responses of 94% (16/17) of NS and WDR neurons and 60% (3/5) of LT neurons. Clonidine facilitated the NMDA-evoked responses in 14% (1/17) of NS, 9% (1/11) of WDR, and 33% (2/6) of LT neurons in the superficial dorsal horn. Idazoxan, an α2AR antagonist, reversed the inhibitory effect of clonidine in 90% (9/10) of neurons, whereas prazosin, an α1-adrenoceptor antagonist with affinity for α2BAR, and α2CAR, were ineffective. We suggest that activation of α2ARs produces a predominantly inhibitory modulation of the NMDA-evoked responses of nociceptive neurons in the medullary dorsal horn.

scholarly journals Microglia–Astrocyte Communication via C1q Contributes to Orofacial Neuropathic Pain Associated with Infraorbital Nerve Injury

2020 ◽  
Vol 21 (18) ◽  
pp. 6834
Author(s):  
Sayaka Asano ◽  
Yoshinori Hayashi ◽  
Koichi Iwata ◽  
Akiko Okada-Ogawa ◽  
Suzuro Hitomi ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Glial Fibrillary Acidic Protein ◽  
Nerve Injury ◽  
Fluorescence Intensity ◽  
Time Window ◽  
Infraorbital Nerve ◽  
Nociceptive Neurons ◽  
Mechanical Hypersensitivity ◽  
Injury Causes ◽  
Immunohistochemical Analyses

Trigeminal nerve injury causes a distinct time window of glial activation in the trigeminal spinal subnucleus caudalis (Vc), which are involved in the initiation and maintenance phases of orofacial neuropathic pain. Microglia-derived factors enable the activation of astrocytes. The complement component C1q, which promotes the activation of astrocytes, is known to be synthesized in microglia. However, it is unclear whether microglia–astrocyte communication via C1q is involved in orofacial neuropathic pain. Here, we analyzed microglia-astrocyte communication in a rat model with infraorbital nerve injury (IONI). The orofacial mechanical hypersensitivity induced by IONI was significantly attenuated by preemptive treatment with minocycline. Immunohistochemical analyses revealed that minocycline inhibited the increase in c-Fos immune-reactive (IR) cells and the fluorescence intensity of both Iba1 and glial fibrillary acidic protein (GFAP) in the Vc following IONI. Intracisternal administration of C1q caused orofacial mechanical hypersensitivity and an increase in the number of c-Fos-IR cells and fluorescence intensity of GFAP. C1q-induced orofacial mechanical hypersensitivity was completely abrogated by intracisternal administration of fluorocitrate. The present findings suggest that the enhancement in the excitability of Vc nociceptive neurons is produced by astrocytic activation via the signaling of C1q released from activated microglia in the Vc following IONI, resulting in persistent orofacial neuropathic pain.

scholarly journals Spinal NGF Restores Opioid Sensitivity in Neuropathic Rats: Possible Role of NGF as a Regulator of CCK-Induced Anti-Opioid Effects

2000 ◽  
Vol 5 (1) ◽  
pp. 49-57 ◽  
Author(s):  
Catherine M Cahill ◽  
Terence J Coderre
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Nerve Injury ◽  
Postnatal Period ◽  
Spontaneous Pain ◽  
Pain Mechanisms ◽  
Nociceptive Neurons ◽  
Nociceptive Transmission ◽  
Chronic Pain Conditions ◽  
Injury Models

The breadth of peripheral effects produced by nerve growth factor (NGF) in nociceptive processing has been well documented. However, less is known about the functional significance of central NGF in nociceptive transmission. The effect of NGF on the nervous system is dependent on the developmental stage. During the prenatal developmental period, NGF is critical for survival of nociceptors; in the postnatal period it regulates the expression of nociceptor phenotype, and in the adult it contributes to pain following an inflammatory insult. The implications for central NGF in the expression and regulation of spinal neuropeptides that are involved in pain mechanisms are reviewed. Knowledge has been gained by studies using peripheral nerve injury models that cause a deprivation of central NGF. These models also give rise to the development of pain syndromes, which encompass spontaneous pain, hyperalgesia and allodynia, routinely referred to as neuropathic pain. These models provide an approach for examining the contribution of central NGF to nociceptive transmission. Chronic pain emanating from a nerve injury is typically refractory to traditional analgesics such as opioids. Recent evidence suggests that supplementation of spinal NGF restores morphine-induced antinociception in an animal model of neuropathic pain. This effect appears to be mediated by alterations in spinal levels of cholecystokinin. The authors hypothesize that NGF is critical in maintaining neurochemical homeostasis in the spinal cord of nociceptive neurons, and that supplementation may be beneficial in restoring and/or maintaining opioid analgesia in chronic pain conditions resulting from traumatic nerve injury.

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