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 microg/kg iv) and the bicyclic cannabinoid CP55,940 (125 microg/kg iv) suppressed noxious heat-evoked activity. Responses evoked by mild pressure in nonnociceptive neurons were not altered by CP55,940 (125 microg/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 microg/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. (+info)
Uninjured C-fiber nociceptors develop spontaneous activity and alpha-adrenergic sensitivity following L6 spinal nerve ligation in monkey.
We investigated whether uninjured cutaneous C-fiber nociceptors in primates develop abnormal responses after partial denervation of the skin. Partial denervation was induced by tightly ligating spinal nerve L6 that innervates the dorsum of the foot. Using an in vitro skin-nerve preparation, we recorded from uninjured single afferent nerve fibers in the superficial peroneal nerve. Recordings were made from 32 C-fiber nociceptors 2-3 wk after ligation and from 29 C-fiber nociceptors in control animals. Phenylephrine, a selective alpha1-adrenergic agonist, and UK14304 (UK), a selective alpha2-adrenergic agonist, were applied to the receptive field for 5 min in increasing concentrations from 0.1 to 100 microM. Nociceptors from in vitro control experiments were not significantly different from nociceptors recorded by us previously in in vivo experiments. In comparison to in vitro control animals, the afferents found in lesioned animals had 1) a significantly higher incidence of spontaneous activity, 2) a significantly higher incidence of response to phenylephrine, and 3) a higher incidence of response to UK. In lesioned animals, the peak response to phenylephrine was significantly greater than to UK, and the mechanical threshold of phenylephrine-sensitive afferents was significantly lower than for phenylephrine-insensitive afferents. Staining with protein gene product 9.5 revealed an approximately 55% reduction in the number of unmyelinated terminals in the epidermis of the lesioned limb compared with the contralateral limb. Thus uninjured cutaneous C-fiber nociceptors that innervate skin partially denervated by ligation of a spinal nerve acquire two abnormal properties: spontaneous activity and alpha-adrenergic sensitivity. These abnormalities in nociceptor function may contribute to neuropathic pain. (+info)
The relationship between submaximal activity of the lumbar extensor muscles and lumbar posteroanterior stiffness.
BACKGROUND AND PURPOSE: Some patients with low back pain are thought to have increased lumbar posteroanterior (PA) stiffness. Increased activity of the lumbar extensors could contribute to this stiffness. This activity may be seen when a PA force is applied and is thought to represent much less force than occurs with a maximal voluntary contraction (MVC). Although MVCs of the lumbar extensors are known to increase lumbar PA stiffness, the effect of small amounts of voluntary contraction is not known. In this study, the effect of varying amounts of voluntary isometric muscle activity of the lumbar extensors on lumbar PA stiffness was examined. SUBJECTS: Twenty subjects without low back pain, aged 26 to 45 years (X=34, SD=5.6), participated in the study. METHODS: Subjects were asked to perform an isometric MVC of their lumbar extensor muscles with their pelvis fixed by exerting a force against a steel plate located over their T4 spinous process. They were then asked to perform contractions generating force equivalent to 0%, 10%, 30%, 50%, and 100% of that obtained with an MVC. Posteroanterior stiffness at L4 was measured during these contractions. RESULTS: A Friedman one-way analysis of variance for repeated measures demonstrated a difference in PA stiffness among all levels of muscle activity. CONCLUSION AND DISCUSSION: Voluntary contraction of the lumbar extensor muscles will result in an increase in lumbar PA stiffness even at low levels of activity. (+info)
Fertility after laparoscopic management of deep endometriosis infiltrating the uterosacral ligaments.
The aim of this study was to evaluate fertility outcome after laparoscopic management of deep endometriosis infiltrating the uterosacral ligaments (USL). From January 1993 to December 1996, 30 patients who presented with no other infertility factors were treated using laparoscopic surgery. The overall rate of intrauterine pregnancy (IUP) was 50.0% (15 patients). Only one of these 15 pregnancies was obtained using in-vitro fertilization techniques (IVF). The cumulative IUP rate for the 14 pregnancies which occurred spontaneously was 48.5% at 12 months (95% confidence interval 28.3-68.7). The rate of spontaneous pregnancies was not significantly correlated with the revised American Fertility Society (rAFS) classification. The rate of IUP was 47.0% (eight cases) for patients with stage I or II endometriosis and 46.1% (six cases) for the patients presenting stage III or IV endometriosis (not significant). These encouraging preliminary results show that in a context of infertility it is reasonable to associate classic treatment for endometriosis (e.g. lysis, i.p. cystectomy, biopolar coagulation of superficial peritoneal endometriotic lesions) with resection of deep endometriotic lesions infiltrating the USL. Apart from the benefit with respect to the pain symptoms from which these patients suffer, it is possible to use laparoscopic surgery with substantial retroperitoneal dissection and enable half of the patients to become pregnant. These results also raise the question of the influence of deep endometriotic lesions on infertility. (+info)
Aberrant neurofilament phosphorylation in sensory neurons of rats with diabetic neuropathy.
Aberrant neurofilament phosphorylation occurs in many neurodegenerative diseases, and in this study, two animal models of type 1 diabetes--the spontaneously diabetic BB rat and the streptozocin-induced diabetic rat--have been used to determine whether such a phenomenon is involved in the etiology of the symmetrical sensory polyneuropathy commonly associated with diabetes. There was a two- to threefold (P < 0.05) elevation of neurofilament phosphorylation in lumbar dorsal root ganglia (DRG) of diabetic rats that was localized to perikarya of medium to large neurons using immunocytochemistry. Additionally, diabetes enhanced neurofilament M phosphorylation by 2.5-fold (P < 0.001) in sural nerve of BB rats. Neurofilaments are substrates of the mitogen-activated protein kinase (MAPK) family, which includes c-jun NH2-terminal kinase (JNK) or stress-activated protein kinase (SAPK1) and extracellular signal-regulated kinases (ERKs) 1 and 2. Diabetes induced a significant three- to fourfold (P < 0.05) increase in phosphorylation of a 54-kDa isoform of JNK in DRG and sural nerve, and this correlated with elevated c-Jun and neurofilament phosphorylation. In diabetes, ERK phosphorylation was also increased in the DRG, but not in sural nerve. Immunocytochemistry showed that JNK was present in sensory neuron perikarya and axons. Motoneuron perikarya and peroneal nerve of diabetic rats showed no evidence of increased neurofilament phosphorylation and failed to exhibit phosphorylation of JNK. It is hypothesized that in sensory neurons of diabetic rats, aberrant phosphorylation of neurofilament may contribute to the distal sensory axonopathy observed in diabetes. (+info)
The lumbosacral dorsal rami of the cat.
The lumbosacral dorsal rami of the cat were studied by gross dissection. The L1-6 dorsal rami form three discrete branches - lateral, intermediate and medial. The lateral branches supply the iliocostalis lumborum and become cutaneous over the back. The intermediate branches ramify in the longissimus lumborum, and are separated from the lateral branches by the lumbar intermuscular septum. The medial branches supply the multifidus and have a constant branch - the nerve to intertransversarii mediales. The L7 dorsal ramus forms only medial and intermediate branches. The S1 and S2 dorsal rami form three branches, the middle of which form the ascending sacral trunk and accessory ascending sacral trunk. The ascending sacral trunk is derived from S1 and S2, the accessory ascending sacral trunk from S2. Both nerves are the exclusive nerve supply of lumbococcygeus. (+info)
Midline medullary depressor responses are mediated by inhibition of RVLM sympathoexcitatory neurons in rats.
Mechanisms underlying the depressor and sympathoinhibitory responses evoked from the caudal medullary raphe (MR) region were investigated in pentobarbital sodium-anesthetized, paralyzed rats. Intermittent electrical stimulation (0.5 Hz, 0.5-ms pulses, 200 microA) of the MR elicited a mixed sympathetic response that consisted of a long-latency sympathoexcitatory (SE) peak (onset = 146 +/- 7 ms) superimposed on an inhibitory phase (onset = 59 +/- 10 ms). Chemical stimulation of the MR (glutamate; Glu) most frequently elicited depressor responses accompanied by inhibition of sympathetic nerve discharge. Occasionally, these responses were preceded by transient pressor and SE responses. We examined the influence of intermittent electrical stimulation (0.5 Hz, 0.5-ms pulses, 25-200 microA) and Glu stimulation of the MR on the discharge of rostral ventrolateral medulla (RVLM) premotor SE neurons. Peristimulus-time histograms of RVLM unit discharge featured a prominent inhibitory phase in response to MR stimulation (onset = 20 +/- 2 ms; duration = 42 +/- 4 ms; n = 12 units). Glu stimulation of the MR reduced blood pressure (-37 +/- 2 mmHg, n = 19) and inhibited the discharge of RVLM SE neurons (15 of 19 neurons). Depressor and sympathoinhibitory responses elicited by chemical and electrical stimulation of the MR region are mediated by inhibition of RVLM premotor SE neurons and withdrawal of sympathetic vasomotor discharge. (+info)
Rostrocaudal progression in the development of periodic spontaneous activity in fetal rat spinal motor circuits in vitro.
Rostrocaudal progression in the development of periodic spontaneous activity in fetal rat spinal motor circuits in vitro. Developmental changes in the periodic spontaneous bursts in cervical and lumbar ventral roots (VRs) were investigated using isolated spinal cord preparations obtained from rat fetuses at embryonic days (E) 13.5-18. 5. Spontaneous bursts were observed in the cervical VR at E13.5-17.5, and in the lumbar VR at E14.5-17.5. Bursts occurrence in the cervical and lumbar VRs was correlated in a 1:1 fashion at E14.5-16. 5. The bursts in the cervical VR preceded those in the lumbar VR at E14.5, but the latter came to precede the former by E16.5. The interval between spontaneous bursts in the lumbar VR was greatly prolonged after spinal cord transection at the midthoracic level at E14.5, whereas that in the cervical VR became significantly longer at E14.5-16.5. These results suggest that the dominant neuronal circuit initiating the spontaneous bursts shifts from cervical to lumbar region during this period. Bath application of a glutamate receptor antagonist, kynurenate (4 mM), had little effect on the spontaneous bursts in either cervical or lumbar VRs at E14.5-15.5. At E16.5, kynurenate abolished the spontaneous bursts in the cervical VR. Concomitant application of kynurenate and strychnine (5 microM), a glycine receptor antagonist, abolished all spontaneous bursts, suggesting that the major transmitter mediating the spontaneous bursts changes from glycine to glutamate in the cervical region by E16.5, but not in the lumbar region during this period. (+info)