Somatosensory evoked potentials in the telencephalon of Atlantic salmon (<Emphasis Type="Italic">Salmo salar</Emphasis>) following galvanic stimulation of the tail

Electric activity in the brain which is time-locked to a given stimulation of the somatosensory system can be recorded as a somatosensory evoked potential (SEP). We investigated whether a galvanic stimulation of the tail base in Atlantic salmon (Salmo salar) would elicit a SEP in the telencephalon. The telencephalon is central in learning and memory, and activity here may be a prerequisite for processing of external stimuli on a cognitive or emotional level. Anaesthetized salmon (n = 11) were subjected to craniotomy and a recording electrode was inserted into the telencephalon. The fish were given stimulations of four intensities, i.e., 2, 5, 10 and 20 mA. A SEP was elicited in the contralateral dorsal telencephalon for all intensities. This result agrees with findings in other fish species. Furthermore, there was a significant difference between the maximum peak amplitude and mean amplitude of the SEP elicited by putative non-noxious (2 mA) and putative noxious (20 mA) stimulation intensities (P < 0.01). The stronger stimulation intensities also tend to introduce longer-latencies components in the SEP. The results added to the body of literature indicates that the exteroceptive senses are represented by processing within the telencephalon of the fish.     

Effects of honokiol and magnolol on acute and inflammatory pain models in mice

The antinociceptive actions of honokiol and magnolol, two major bioactive constituents of the bark of Magnolia officinalis, were evaluated using tail-flick, hot-plate and formalin tests in mice. The effects of honokiol and magnolol on the formalin-induced c-Fos expression in the spinal cord dorsal horn as well as motor coordination and cognitive function were examined. Data showed that honokiol and magnolol did not produce analgesia in tail-flick, hot-plate paw-shaking and neurogenic phase of the overt nociception induced by intraplantar injection of formalin. However, honokiol and magnolol reduced the inflammatory phase of formalin-induced licking response. Consistently, honokiol and magnolol significantly decreased formalin-induced c-Fos protein expression in superficial (I-II) laminae of the L4-L5 lumbar dorsal horn. However, honokiol and magnolol did not elicit motor incoordination and memory dysfunction at doses higher than the analgesic dose. These results demonstrate that honokiol and magnolol effectively alleviate the formalin-induced inflammatory pain without motor and cognitive side effects, suggesting their therapeutic potential in the treatment of inflammatory pain.     

Testosterone reduces responsiveness to nociceptive stimuli in a wild bird

The hormone testosterone (T) is involved in the control of aggressive behavior in male vertebrates. T enhances the frequency and intensity of aggressive behaviors during competitive interactions among males. By promoting high-intensity aggression, T also increases the risk of injury and presumably the perception of painful stimuli. However, perception of painful stimuli during fights could counteract the expression of further aggressive behavior. We therefore hypothesize that one function of T during aggressive interactions is to reduce nociception (pain sensitivity). Here, we experimentally document that T indeed reduces behavioral responsiveness to a thermal painful stimulus in captive male house sparrows (Passer domesticus). Skin nociception was quantified by foot immersion into a hot water bath, a benign thermal stimulus. Males treated with exogenous testosterone left their foot longer in hot water than control birds. Conversely, males in which the physiological actions of testosterone were pharmacologically blocked withdrew their foot faster than control birds. Testosterone might exert its effects on pain sensitivity through conversion into estradiol in the dorsal horn of the spinal cord. Decreased nociception during aggressive encounters may promote the immediate and future willingness of males to engage in high-intensity fights.     

Neurochemical Characterization of Extracellular Serotonin in the Rostral Ventromedial Medulla and Its Modulation by Noxious Stimuli

Abstract: Using in vivo microdialysis, we have characterized serotonin release from the rostral ventromedial medulla of the freely moving rat. Addition of tetrodotoxin or removal of calcium from the dialysis solution diminished the dialysate serotonin content, suggesting that spontaneous, calcium channel- and sodium channel-dependent neuronal release mechanisms contribute to the extracellular serotonin collected from the rostral ventromedial medulla. Extracellular serotonin concentration was increased by depolarization (with 100 m M potassium) and by the local administration of either a reuptake blocker (citalopram), a monoamine oxidase inhibitor (pargyline), or amphetamine. Serotonin release was reduced significantly by 8-hydroxy-2-(di- n -propylamino)tetralin, suggesting that serotonin_1A receptors may regulate release from rostral ventromedial medulla neurons. Because the basal serotonin concentration in the rostral ventromedial medulla was approximately twofold higher than that collected from the rostral ventrolateral medulla, a region that contains serotonin terminals but many fewer cell bodies, the possibility of release of serotonin from rostral ventromedial medulla neurons is discussed. Finally, intraplantar formalin injection significantly increased serotonin release, suggesting that this neurotransmitter contributes to nociceptive modulation by regulating the outflow of the rostral ventromedial medulla neurons.     

Antinociceptive and anti-inflammatory activities of butein in different nociceptive and inflammatory mice models

BackgroundAround 30% world population affected by acute and chronic pain due to inflammation and accidental injuries. Pain is a uncomfortable sensation and it reduce the patients’ life quality.ObjectiveThe present exploration focuses to explore the beneficial effects of butein on the different chemical and thermal-provoked nociceptive and inflammatory mice models.MethodologyThe nociception was induced to the Swiss mice using different chemical (formalin, acetic acid, glutamate, and capsaicin) and thermal (hot plate and tail immersion) methods. the mice were supplemented with 10, 15, and 20 mg/kg of butein and respective standard drugs like morphine, diclofenac sodium, and dexamethasone. The anti-inflammatory effects of butein was studied using carrageenan-provoked inflammation in mice.ResultsThe present findings clearly demonstrated that the butein was substantially lessened the different thermal and chemical provoked nociception in mice. The carrageenan-triggered paw edema and inflammatory cell infiltrations were appreciably suppressed by the butein treatment. The TNF-α, IL-1β, and IL-6 levels in the carrageenan-induced mice were effectively depleted by the butein.ConclusionAltogether, the present findings evidenced the potent antinociceptive and anti-inflammatory properties of the butein in different nociceptive mice models.     

Nitric Oxide Regulates Substance P Release from Rat Spinal Cord Synaptosomes

Abstract: In order to determine whether nitric oxide (NO) acts directly upon nerve terminals to regulate the synaptic transmission at the level of spinal cord, effects of NO-donors on release of substance P (SP) and glutamic acid (Glu) were investigated by superfusion of synaptosomes prepared from the rat spinal cord. Basal levels of endogenous SP and Glu release were 5.99 ± 2.50 fmol/min/mg of protein and 26.2 ± 4.8 pmol/min/mg of protein, respectively. Exposure to a depolarizing concentration of KCI evoked 2.7- and 3.8-fold increases in SP and Glu release in a calcium-dependent manner, respectively. Sodium nitroprusside (NP) caused a reduction in the depolarization-evoked overflow of SP in a concentration-dependent manner without affecting its basal release, although it failed to affect either basal or evoked release of Glu. The reduction in SP overflow was also observed by the perfusion with S -nitroso- N -acetyl-penicillamine or membrane-permeable cyclic GMP, but not with cyclic AMP. NP caused the concentration-dependent increases in cyclic GMP levels in synaptosomes. Together with reports that excitatory amino acids stimulate NO synthase and release NO in the spinal cord, these data suggest that there may be an interaction between nerve terminals containing Glu and SP, and that NO may directly participate in the regulation of synaptic transmission in SP-containing nerve terminals, which may be mediated through the activation of guanylate cyclase and the increase in cyclic GMP levels.     

The glutamate transporter GLAST is involved in spinal nociceptive processing

GLAST and GLT-1 are the most abundant glutamate transporters in the CNS and protect neurons from glutamate neurotoxicity. Here, we investigated the role of GLAST in spinal nociceptive processing. GLAST protein expression was not altered after treatment of rats with either formalin or zymosan. Surprisingly, knock-down of GLAST in the spinal cord using antisense-oligonucleotides decreased glutamate concentrations in cerebrospinal fluid (CSF) and reduced the nociceptive behaviour in the rat formalin assay. However, it did not influence thermal hyperalgesia in the zymosan-induced paw inflammation model indicating that GLAST is associated with spontaneous rather than inflammatory nociception. Mechanisms that might explain the decreased response in the formalin assay may include compensatory activation of other glutamate transporters, inhibition of glutamate release or disturbance of glutamate recycling. In conclusion, these data suggest that inhibition of GLAST expression in the spinal cord reduces excitatory synaptic activity and thereby spontaneous responses after nociceptive stimulation of the paw.     

Dynamic Processing of Nociception in Cortical Network in Conscious Rats: A Laser-evoked Field Potential Study

(1) Field potential study in conscious rats provides a convenient and effective animal model for pain mechanism and pharmacological research. However, the spatial-temporal character of nociception processing in cortex revealed by field potential technique in conscious rats remains unclear. (2) In the present study, multi-channel field potentials evoked by noxious laser stimulation applied to the hind paw of conscious rats were recorded through 12 chronically implanted skull electrodes. Independent component analysis (ICA) was used to remove possible artifacts and to extract the specific nociception-related component. (3) Two fast sharp responses and one slow blunt response were evoked by noxious laser stimulation. Systemic morphine (5 mg/kg, i.p.) preferentially attenuated the amplitude of the slow blunt response while had no significant effect on the first two sharp responses. ICA revealed that those responses came from activities of contralateral anterior parietal area, medial frontal area and posterior parietal area. A movement artifact was also detected in this study. Partial directed coherence (PDC) analysis showed that there were changes of information flows from medial frontal and posterior parietal area to anterior parietal area after noxious laser stimulation. (4) Characterization of the spatio-temporal responses to noxious laser stimulation may be a valuable model for the study of pain mechanisms and for the assessment of analgesia.     

c-fos expression in trigeminal spinal nucleus after electrical stimulation of the hypoglossal nerve in the rat

The expression of the immediate early gene, c-fos, was used to determine the distribution of brainstem neurons activated by stimulation of the distal hypoglossal nerve (XIIn) trunk. The traditional view of the XIIn is one of purely motor function; however, stimulation of XIIn excites neurons in the trigeminal spinal nucleus. The rationale for this study was to use c-fos expression as a marker for postsynaptic activity to define the pattern of brainstem neurons excited by XIIn stimulation. It was further hypothesized that if the afferent fibers that course within XIIn supply deep lingual tissues, then c-fos expression after direct stimulation of XIIn should display a pattern similar to that seen after chemical irritant stimulation of the deep tongue muscle. In barbiturate-anesthetized male rats electrical stimulation of XIIn produced a significant increase in Fospositive neurons in the dorsal paratrigeminal nucleus (dPa5) and laminae I-II of caudal subnucleus caudalis (Vc) and upper cervical dorsal horn. Mustard oil injection into the deep tongue muscle also produced an increase in c-fos expression in dPa5; however, the highest density of expression occurred in laminae I-II at the dorsomedial aspect of rostral Vc. Both electrical stimulation of XIIn and mustard oil stimulation of the deep tongue increased c-fos expression in the caudal ventrolateral medulla, an autonomic relay nucleus. These results suggest that one site of innervation for afferent fibers that travel within the distal trunk of XIIn is to supply the deep tongue muscle and to terminate in the dPa5. A second group of postsynaptic neurons activated only by XIIn stimulation was located in lamina I-II in caudal portions of Vc and upper cervical dorsal horn, a laminar distribution consistent with a role for XIIn afferents in sensory or autonomic aspects of lingual function.