Actions of narcotic analgesics and antagonists on spinal units responding to natural stimulation in the cat

1979 ◽  
Vol 57 (6) ◽  
pp. 652-663 ◽  
Author(s):  
O. Calvillo ◽  
J. L. Henry ◽  
R. S. Neuman

Morphine and morphine-related agents were applied by microiontophoresis in the lumbar spinal cord of spinal cats to single units classified on the basis of their responses to natural cutaneous or proprioceptive stimulation. Opiate application had a current-dependent depressant effect on the ongoing activities of about one-third of the units tested. This effect was observed in laminae I and IV–VI, but only with units responding to noxious cutaneous stimuli: the nociceptive responses were themselves depressed. Excitatory and inhibitory responses to glutamate and γ-aminobutyric acid, respectively, were also depressed. Intravenous administration of the opiates at doses reported to produce analgesia in the cat also depressed only units responding to noxious cutaneous stimuli, including their nociceptive responses. This depression could be reversed by either the iontophoretic application (100 nA) or the intravenous administration (0.1–0.8 mg/kg) of naloxone. These results are interpreted as further evidence that the analgesic effects of opiates are at least partly due to an action at the spinal level.

1975 ◽  
Vol 53 (3) ◽  
pp. 423-432 ◽  
Author(s):  
J. L. Henry ◽  
K. Krnjević ◽  
M. E. Morris

When applied by microiontophoresis, substance P (sP) had a strong, but slow and prolonged excitatory action on nearly half the neurones tested in the lumbar spinal cord of cats. Motoneuronal antidromic field potentials only occasionally showed a significant effect of sP. Cerebral cortical neurones in cats and rats were much less readily excited than spinal interneurones. Some unresponsive units showed evidence of a depressant effect of sP. Although sP may have a significant function in central afferent pathways, it is not likely to be a quickly-acting synaptic transmitter.


2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Katarzyna Popiolek-Barczyk ◽  
Ewelina Rojewska ◽  
Agnieszka M. Jurga ◽  
Wioletta Makuch ◽  
Ferenz Zador ◽  
...  

Nociceptin/orphanin FQ (N/OFQ) antinociception, which is mediated selectively by the N/OFQ peptide receptor (NOP), was demonstrated in pain models. In this study, we determine the role of activated microglia on the analgesic effects of N/OFQ in a rat model of neuropathic pain induced by chronic constriction injury (CCI) to the sciatic nerve. Repeated 7-day administration of minocycline (30 mg/kg i.p.), a drug that affects microglial activation, significantly reduced pain in CCI-exposed rats and it potentiates the analgesic effects of administered N/OFQ (2.5–5 μg i.t.). Minocycline also downregulates the nerve injury-induced upregulation of NOP protein in the dorsal lumbar spinal cord. Ourin vitrostudy showed that minocycline reducedNOPmRNA, but not protein, level in rat primary microglial cell cultures. In [35S]GTPγS binding assays we have shown that minocycline increases the spinal N/OFQ-stimulated NOP signaling. We suggest that the modulation of the N/OFQ system by minocycline is due to the potentiation of its neuronal antinociceptive activity and weakening of the microglial cell activation. This effect is beneficial for pain relief, and these results suggest new targets for the development of drugs that are effective against neuropathic pain.


1998 ◽  
Vol 7 (3) ◽  
pp. 227-238 ◽  
Author(s):  
Jean C. Bés ◽  
Jean Tkaczuk ◽  
Kimberly A. Czech ◽  
Mathieu Tafani ◽  
Raymond Bastide ◽  
...  

The control of chronic pain through transplantation of chromaffin cells has been reported over the past few years. Analgesic effects are principally due to the production of opioid peptides and catecholamines by chromaffin cells. Clinical trials have been reported with allografts consisting of whole-tissue fragments implanted into the subarachnoid space of the lumbar spinal cord (14,19,36). In the present study, allogeneic grafts were successfully used to control chronic pain in two patients over a period of 1 yr based on patient reported pain scores, morphine intake, and CSF levels of Met-enkephalin. Macroscopic examination at autopsy located the transplanted tissue fragments in the form of multilobulated nodules at the level of the spinal axis and cauda equina. Immunocytochemical microscopy showed neuroendocrine cells are positive for chromagranin A (CGA), and enzymes tyrosine hydroxylase (TH) and dopamine-β-hydroxylase (DβH). The results suggest that there is a relationship between analgesic effect, Met-enkephalin levels in CSF, and the presence of chromaffin cells surviving in spinal subarachnoid space.


2020 ◽  
Vol 16 ◽  
pp. 174480692096947
Author(s):  
Jeong-Yun Lee ◽  
Grace J. Lee ◽  
Ayumi Nakamura ◽  
Pa Reum Lee ◽  
Yeajin Kim ◽  
...  

The endocannabinoid system (ECS) is known to modulate not only food intake but also pain, especially via the cannabinoid type 1 receptor (CB1R) expressed throughout the central nervous system and the peripheral tissues. Our previous study demonstrated that fasting produces an analgesic effect in adult male mice, which is reversed by intraperitoneal (i.p.) administration of CB1R antagonist (SR 141716). In the present study, we further examined the effect of CB1R expressed in the peripheral tissues. In the formalin-induced inflammatory pain model, i.p. administration of peripherally restricted CB1R antagonist (AM 6545) reversed fasting-induced analgesia. However, intraplantar administration of SR 141716 did not affect fasting-induced analgesia. Furthermore, mRNA expression of CB1R did not change in the formalin model by fasting in the dorsal root ganglia. The formalin-induced c-Fos expression at the spinal cord level was not affected by fasting, and in vivo recording from the superficial dorsal horn of the lumbar spinal cord revealed that fasting did not affect formalin-induced neural activity, which indicates minimal involvement of the spinal cord in fasting-induced analgesia. Finally, when we performed subdiaphragmatic vagotomy to block the hunger signal from the gastrointestinal (GI) system, AM 6545 did not affect fasting-induced analgesia, but SR 141716 still reversed fasting-induced analgesia. Taken together, our results suggest that both peripheral and central CB1Rs contribute to fasting-induced analgesic effects and the CB1Rs in the GI system which transmit fasting signals to the brain, rather than those in the peripheral sensory neurons, may contribute to fasting-induced analgesic effects.


2018 ◽  
Vol 46 (05) ◽  
pp. 323-329 ◽  
Author(s):  
Nele Ondreka ◽  
Sara Malberg ◽  
Emma Laws ◽  
Martin Schmidt ◽  
Sabine Schulze

SummaryA 2-year-old male neutered mixed breed dog with a body weight of 30 kg was presented for evaluation of a soft subcutaneous mass on the dorsal midline at the level of the caudal thoracic spine. A further clinical sign was intermittent pain on palpation of the area of the subcutaneous mass. The owner also described a prolonged phase of urination with repeated interruption and re-initiation of voiding. The findings of the neurological examination were consistent with a lesion localization between the 3rd thoracic and 3rd lumbar spinal cord segments. Magnetic resonance imaging revealed a spina bifida with a lipomeningocele and diplomyelia (split cord malformation type I) at the level of thoracic vertebra 11 and 12 and secondary syringomyelia above the aforementioned defects in the caudal thoracic spinal cord. Surgical resection of the lipomeningocele via a hemilaminectomy was performed. After initial deterioration of the neurological status postsurgery with paraplegia and absent deep pain sensation the dog improved within 2 weeks to non-ambulatory paraparesis with voluntary urination. Six weeks postoperatively the dog was ambulatory, according to the owner. Two years after surgery the owner recorded that the dog showed a normal gait, a normal urination and no pain. Histopathological diagnosis of the biopsied material revealed a lipomeningocele which confirmed the radiological diagnosis.


1996 ◽  
Vol 16 (2) ◽  
pp. 106-111 ◽  
Author(s):  
Ming Zhou ◽  
Noboru Goto ◽  
Chen Zhang ◽  
Wei Tang

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Marco Bonizzato ◽  
Nicholas D. James ◽  
Galyna Pidpruzhnykova ◽  
Natalia Pavlova ◽  
Polina Shkorbatova ◽  
...  

AbstractA spinal cord injury usually spares some components of the locomotor circuitry. Deep brain stimulation (DBS) of the midbrain locomotor region and epidural electrical stimulation of the lumbar spinal cord (EES) are being used to tap into this spared circuitry to enable locomotion in humans with spinal cord injury. While appealing, the potential synergy between DBS and EES remains unknown. Here, we report the synergistic facilitation of locomotion when DBS is combined with EES in a rat model of severe contusion spinal cord injury leading to leg paralysis. However, this synergy requires high amplitudes of DBS, which triggers forced locomotion associated with stress responses. To suppress these undesired responses, we link DBS to the intention to walk, decoded from cortical activity using a robust, rapidly calibrated unsupervised learning algorithm. This contingency amplifies the supraspinal descending command while empowering the rats into volitional walking. However, the resulting improvements may not outweigh the complex technological framework necessary to establish viable therapeutic conditions.


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