Sympathetic reflex responses presumably specific for nociceptive stimulation

1. In superficially anaesthetized and in unanaesthetized decerebrate cats, tetanic stimulation of A or A + C afferent fibres of the tibial nerve evoked in renal and inferior cardiac nerves a three-phasic change of activity, which consisted of a short powerful burst of discharges, followed by an inhibitory pause and then, by a moderate excitation. When such a command appeared in sympathetic nerves, reflex rising of systemic arterial pressure was extremely fast. 2. The latencies of the three-phasic command and of the so-called very late A response are almost the same. The very late A response is evident if the central nervous system is in the same state as when repetitive stimulation of A afferents evokes the three phasic command in sympathetic nerves and a steep rise of systemic arterial pressure. This permits the assumption that the very late A response reflects the excitation of just those central structures that on repetitive stimulation organize the three-phasic command. 3. A command of this kind is shown to ensure the optimal-time-control of the heart and blood vessels. Such a control (three-phasic command) is supposed to be evoked by nociceptive stimulation, i.e., to be specific for the defence reaction.     

Presynaptic excitability changes of group Ia fibres to muscle nociceptive stimulation in humans

Tonic muscle nociceptive discharge evoked chemically from the foot extensor digitorum brevis muscle in man produces a depression of Ia excitation and Ib inhibition of the soleus (Sol) motoneurones (Mns). The possibility that both these changes partly result from presynaptic inhibition of Ia fibres projecting to Sol Mns and to interneurones mediating group I non-reciprocal inhibition is tested. Convergence of Ia fibres on these interneurones was deduced from evidence that reducing the excitatory effect of the extensor Ia fibres (by potentiation of their presynaptic inhibition) resulted in Ib disinhibition. Nociceptive-induced potentiation of Ia presynaptic inhibition was deduced from the following congruent results obtained by two independent methods: (1) depression of heteronymous Ia monosynaptic facilitation of the quadriceps muscle to Sol Mns; (2) potentiation of presynaptic inhibition of Sol Ia fibres evoked by mechanical activation of the tibialis anterior primary spindle afferents. It is concluded that nociceptive volleys arising from dorsal foot muscles facilitate the activity of interneurones intercalated in pathways responsible for presynaptic inhibition of Sol Ia fibres. It is also proposed that the same Ia presynaptic inhibition depresses the excitability of interneurones mediating group I non-reciprocal inhibition, thus resulting in Ib disinhibition of Sol Mns.     

Convergence of nociceptive and non-nociceptive inputs onto spinal reflex pathways to the tibialis anterior muscle in humans

To investigate whether the familial clustering of cutaneous melanoma is consistent with Mendelian inheritance of a major autosomal gene, maximum likelihood segregation analyses were performed in a population-based sample of 1,912 families ascertained through a proband with melanoma diagnosed in Queensland between 1982 and 1990. Analyses were performed with the S.A.G.E. statistical package, using the REGTL program for a binary trait with a variable age of onset. We sought medical confirmation for all family members reported to have had melanoma, and only medically verified cases among relatives were included in the analyses. The hypothesis of codominant Mendelian inheritance gave a significantly better fit to the data than either dominant or recessive Mendelian inheritance, or environmental transmission. Overall, both Mendelian inheritance of a single major gene, and purely environmental transmission were rejected (P < 0.001). In both the single major gene and environmental models, there was strong evidence of familial dependence in melanoma occurrence (P < 0.001). These results are consistent with reported genetic heterogeneity in melanoma inheritance and suggest that other familial factors, such as pigmentation, skin type, and sun exposure habits, may play an important role in the familial clustering of melanoma.     

Spinal trigeminal tractotomy and nociceptive reactions evoked by tooth pulp stimulation in the cat

The effect of transection of the descending root of the spinal trigeminal tract on nociceptive and aversive reactions evoked by stimulation of the tooth pulp nerve was studied in cats. The transection was performed 1-1.5 mm caudally to the obex. 1. The nociceptive reaction, characterized by wide opening of the jaw, dorsiflexion and rotation of the head and by signs of affective behaviour, remained unchanged after transection of the descending root of the trigeminal nerve (n = 6). 2. The instrumental escape reaction was elaborated in three cats before transection of the descending root of the trigeminal nerve and in three cats after transection. The escape reaction was retained after transection of the descending root and the speed of learning to escape the tooth pulp stimulation did not significantly differ in these two groups of animals. 3. It is to be concluded that the transection of the descending root of the spinal trigeminal tract in the cat does not result in dental analgesia.     

Morphine application to peripheral tissues modulates nociceptive jaw reflex

This study assessed the effect of peripherally applied opioids on the electromyographic activity reflexly evoked in digastric and masseter muscles by injection of the small-fiber excitant and inflammatory irritant mustard oil (MO) into the temporomandibular joint. In 39 anaesthetized rats, local pretreatment of joint tissues with morphine (15 nmol) significantly depressed the jaw muscle responses compared with saline, and the depression was antagonized by simultaneous local injection of the opiate antagonist naloxone (2.7 nmol); systemic morphine pretreatment (15 nmol, i.v.) did not influence the muscle responses. The naloxone-reversible depression of the MO-evoked muscle responses by local, but not systemic morphine, supports the presence of peripheral opioid receptors that may have a role in modulating nociceptive responses.     

Spinal serotonergic receptors mediate facilitation of a nociceptive reflex by subcutaneous formalin injection into the hindpaw in rats

It is documented that spinal nociceptive transmission receives descending facilitatory and inhibitory modulation from supraspinal structures. The rostral ventral medulla (RVM), including the nucleus raphe magnus (NRM), nuclei reticularis gigantocellularis (NGC) and gigantocellularis pars alpha (NGCalpha), is the major bulbar relay of descending modulatory influences. Pharmacological studies show that facilitation of a spinal nociceptive tail-flick (TF) reflex induced by stimulation in the NGC and NGCalpha is mediated by spinal serotonergic receptors. The present series of experiments provide evidence that activation of spinal serotonergic systems are critical for both induction and maintenance of secondary hyperalgesia induced by subcutaneous injection of formalin into one hindpaw. Subcutaneous injection of formalin produced facilitation of tail withdrawal (mechanical) and the TF reflex (thermal). Facilitatory effects persisted for at least 30 min. Peripheral blockade of the activity by local injection of a hydrophilic lidocaine derivative (QX-314, 5%) into the injected hindpaw abolished both mechanical and thermal facilitation, indicating that peripheral input is important to maintain long-lasting facilitation. Intrathecal application of a serotonergic receptor antagonist methysergide at a dose (64 nmol) which completely blocked descending facilitation produced by electrical- or chemical-stimulation in the NGC and NGCalpha also significantly attenuated or completely abolished facilitation of tail withdrawal and the TF reflex induced by formalin. Methysergide was effective whether the injection was performed before or after the formalin injection. These results suggest that activation of descending facilitatory serotonergic influences by a prolonged noxious stimulation could contribute to secondary hyperalgesia observed at the tail.     

Temporal integration of acoustic stimulation obtained in reflex inhibition in rats and humans.

Investigated whether inhibition provided by initial stimuli of various durations conforms to established temporal integration functions. Initial stimuli (S1) were noise bursts varying in duration (2, 20, or 200 msec) and intensity (55 or 85 db). Eliciting stimuli (S2) for 6 Holtzman rats were intense tone bursts, which elicited the acoustic startle reflex, and for 9 19–24 yr old humans were electrotactile stimuli to the forehead, which elicited the eye blink. Findings reveal that inhibition was greater with the 85-db S1 stimulus and increased linearly with log increases in duration. Data suggest that the acoustic substrate for reflex inhibition has a long-time constant. There was one exception to this general finding. For 7 human Ss, inhibition declined when the duration of the 85-db S1 was increased from 20 to 200 msec. Postexperimental questioning and video monitoring suggest that this anomaly resulted from a reflex-enhancing arousal process. (38 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Transient and steady-state electroretinograms and visual evoked potentials to pattern and uniform-field stimulation in humans

I recorded simultaneously transient and steady-state electroretinograms (ERGs) and visual evoked potentials (VEPs) in response to pattern and uniform-field stimulation in 21 normal subjects, in order to study their physiological characteristics. ERGs and VEPs to pattern stimulation (P-ERGs and P-VEPs, respectively) showed different physiological features from those to uniform-field stimulation (U-ERGs and U-VEPs, respectively). With transient stimulation at a rate of 1Hz for both pattern and uniform-field stimulation, the b-wave latency of U-ERG tended to be shorter than that of P-ERG, while the P100 latency of P-VEP was significantly shorter than that of U-VEP. With steady-state stimulation at a rate of 4Hz for pattern stimulation and of 8Hz for uniform-field stimulation, the phase analysis revealed the first (1F) and the second (2F) harmonics as stable components for the U-ERG and U-VEP, while only 2F harmonic was a stable component for the P-ERG and P-VEP. The phase values of these components were different each other, and the maximal amplitude of the ERGs was shown by the 1F of U-ERG while that of the VEPs was shown by the 2F of P-VEP. These results suggest that the pattern and uniform-field stimulation allows us to separate pattern (contrast)-specific responses from luminance-specific responses both in ERGs and VEPs. Four patients with optic atrophy showed normal U-ERG while all of them showed abnormal P-ERG, U-VEP and P-VEP except one, who showed normal U-VEP. P-ERGs and P-VEPs may offer the information about the proximal inner retinal layer (or the ganglion cells) and the contrast channel of the visual cortex. U-ERGs and U-VEPs may be useful in evaluating the functions of the preganglionic cell activity in the retina and the luminance channel of the visual cortex. Therefore, simultaneous recording of ERGs and VEPs to pattern and uniform-field stimulation under both transient and steady-state conditions increase the diagnostic value of electrophysiologic testing in the visual pathways.     

Cutaneous nociceptive facilitation of Ib heteronymous pathways to lower limb motoneurones in humans

The effects of tonic pain stimulation on heteronymous Ib pathways from the gastrocnemius medialis (GM) to the soleus (Sol) and to the quadriceps (Q) muscles were investigated in four healthy human subjects. Tonic pain stimulation was performed by subcutaneous injection of 0.5 mg levo-ascorbic acid or vitamin C (L-LAS) in a volume of 0.5 ml on the dorsal surface of the ipsilateral foot. The mean curve of L-AS-induced pain sensation showed a steep rising phase reaching maximum intensity at 2-3 min, followed by a slow decay phase lasting about 15-20 min. Between about 5 and 20 min after injection, there was evidence of pure pain stimulation due to chemical activation of free nerve endings. During this interval, significant potentiation of Ib inhibition from GM to both Sol and Q motoneurones was observed. The time-course of these Ib heteronymous changes paralleled that of subjective pain sensation. These findings demonstrate that nociceptive discharge modifies the gain of Ib heteronymous effects in humans. Since the man function of these Ib pathways is to coordinate activity of muscles operating at different joints, it is suggested that nociceptive input may change muscle synergies by selecting specific subpopulations of Ib interneurones, thus contributing to establish appropriate adaptive motor strategies.     

Cerebral evoked responses to gastrointestinal stimulation in humans

Recent advances have permitted recording of evoked potentials (EPs) in response to electrical and mechanical stimulation of the gastrointestinal (GI) organs via methods used primarily in clinical neurophysiology. Current research involving stimulation of the esophagus, rectum, and colon, and recording the corresponding responses on the scalp, is being practiced in only a few laboratories. This review examines the engineering aspects of recording EPs, such as characteristics of the stimuli, placement of stimulus electrodes in the GI tract, and enhancement of evoked potential signals. We also discuss the physiological concepts involved in the generation of EPs, and how these compare with somatosensory evoked responses. Current experimental techniques employed by various investigators and results reported from their laboratories are compared. We believe that cerebral EPs to GI stimulation could be useful in studying a number of pathophysiological conditions such as gastroesophageal reflux disease, diffuse esophageal spasm, chronic inflammatory bowel disorders, chronic abdominal pain, and irritable bowel syndrome, among others. We hope that the present review will generate interest in the use of EPs arising out of GI stimulation, aiding in understanding their physiological implications in healthy subjects and in GI disorders.     

Latent structure of strategies used to cope with nociceptive stimulation.

Investigated the latent cognitive structure of 32 undergraduates' perceptions of coping strategies used by 50 college students exposed to a cold pressor test or a muscle ischemia task, using multidimensional scaling (MDS). The resulting strategy clusters (e.g., behavioral activity, pleasant imaginings) were grouped into sensation acknowledging, coping relevance, and cognitive/behavioral dimensions. Using different methodology and MDS analysis, 22 undergraduates' perceptions of the 3 coping strategies were examined. There was close correspondence between the resulting dimensions and those of the 1st sample. Results show that Ss preferred strategies that ignored pain sensations and suggest a method for assessing relative efficiency of coping strategies for pain. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Laser irradiation abates neuronal responses to nociceptive stimulation of rat-paw skin

The effects of diode laser irradiation on peripheral nerves was examined by monitoring neuronal discharges elicited by application of various stimuli to the hind-paw skin of rats. Neuronal discharges elicited by brush, pinch, cold, and/or heat stimulation, as well as chemical stimulation by injection of turpentine (0.1 ml, SC) were recorded from L5 dorsal roots in urethane-anesthetized rats. Diode laser irradiation (830 nm, 40 mW, 3 min, continuous wave) of the saphenous nerve exposed from the muscle of the lower leg significantly inhibited neuronal discharges elicited by pinch (68.4 +/- 6.5%), cold (45.4 +/- 9.2%), and heat stimulation (49.2 +/- 11.3%). Neuronal discharges induced by brush stimulation (104.3 +/- 4.7%) were not affected by laser irradiation. Injection of turpentine, a chemical irritant, into the hind-paw skin (0.1 ml, SC) elicited neuronal discharges in the ipsilateral dorsal root, and these discharges were significantly inhibited or abolished by laser irradiation. In 6- to 7-week-old rats treated neonatally with capsaicin (10 mg/kg, SC), injection of turpentine into the hind-paw skin did not elicit neuronal discharges and laser irradiation did not affect the background discharges. These data suggest that laser irradiation may selectively inhibit nociceptive neuronal activities.     

Corticospinal direct response to transcranial magnetic stimulation in humans

The corticospinal motor evoked potential (MEP) response to transcranial magnetic stimulation of the motor cortex was investigated in comparison with the direct (D) response to electrical stimulation of the exposed motor cortex from the spinal epidural space in 7 neurologically normal patients during brain tumor surgery. The D response during operation was obtained by transcranial magnetic stimulation of the scalp over the areas of the cerebral motor cortex, the hand or arm areas. The magnetic induced D response showed a conduction velocity of 50.5-72.7 m/sec and was resistant to anesthesia and unaffected by muscle relaxants and tolerant to high frequency (500 Hz) paired magnetic stimulus, and the latencies of magnetic MEPs corresponded to those with direct electrical stimulation. Thus, recordings of the D response by transcranial magnetic stimulation are useful for not only identifying the location of the motor cortex during intracranial surgery but also for non-invasive recording of pyramidal tract activity during extracranial surgery under general anesthesia.     

Changes in reflex excitability following isometric contraction in humans

The dose rate at which cells are exposed to X-rays may influence the nature of induced mutations. To investigate this, the molecular spectra were determined at the HPRT gene in a hamster (V79) and a human (WI-L2-NS) cell line after the same total dose of X-rays has been administered at either a low dose rate (LDR; 3.33 mGy/min) or a high dose rate (HDR; 1.24-1.4 Gy/min) X-irradiation. Mutational spectra appeared similar, the fraction of mutants carrying deletions ranging between 59%-66% for the V79 strain and between 64%-75% for the WI-L2-NS strain, and independent of the irradiation conditions. The data indicate no effect of ongoing repair processes under LDR conditions on the kind of induced mutations in mammalian cells.     

Topical ondansetron attenuates nociceptive and inflammatory effects of intradermal capsaicin in humans

Topical application of the 5-HT3 receptor antagonist ondansetron (50-250 microg) delivered in a pluronic lecithin organogel vehicle (PLO, 0.5 ml) produced dose-dependent attenuation of nociceptive and inflammatory effects of intradermally injected capsaicin (10 microg/10 microl) in humans. Significant, dose-dependent analgesic effects were produced by 100 microg and 250 microg doses of ondansetron; these doses also reduced mechanical hyperalgesia produced by capsaicin. However, only 250 microg dose of ondansetron diminished capsaicin-induced inflammatory flare.     

Isoflurane and sevoflurane augment norepinephrine responses to surgical noxious stimulation in humans

BACKGROUND: Suppression of hypertensive response to noxious stimulation by volatile anesthetics may be a result of suppression of the stimulation-induced norepinephrine response or that of the cardiovascular response to catecholamines, or both. The suppression of the cardiovascular response is established, but that of norepinephrine response has not been confirmed. The authors hypothesized that the suppression of cardiovascular response but not that of norepinephrine response plays a major role in suppressing the noxious stimulation-induced hypertensive response by volatile anesthetics. METHODS: Forty healthy donors for living-related liver transplantation were allocated to four groups: receiving 1.2% (end-tidal) isoflurane in oxygen and nitrogen, 2.0% isoflurane, 1.7% sevoflurane, or 2.8% sevoflurane. The intraoperative plasma norepinephrine and epinephrine concentrations, arterial blood pressure and pulse rate were measured for the first 15 min of surgery and were compared with the preoperative values. RESULTS: Norepinephrine and epinephrine concentrations both increased intraoperatively in all four groups. The values of maximum increase and area under the concentration-versus-time curve of norepinephrine were greater in the high dose groups of both anesthetics. The intraoperative blood pressure did not differ by different doses of anesthetics, and the degree of increase of blood pressure was not proportional to the plasma catecholamine concentrations. CONCLUSION: The effects of isoflurane and sevoflurane on the surgical noxious stimulation-induced norepinephrine response were inversely proportional to the dose. The suppression of noxious stimulation-induced blood pressure response by anesthetics that were studied may be the result of suppression of the responses of vascular smooth muscle and myocardium to catecholamines.     

Spinal cord stimulation in multiple sclerosis: clinical results

Clinical results of spinal cord stimulation by means of epidural electrodes are reported in 19 patients with multiple sclerosis. On temporary stimulation with percutaneous electrodes, significant improvement in mobility occurred in 27.7% of 18 patients and the same number showed improved sensory function. Only one of 13 patients with severe upper limb ataxia improved. The major response, both in terms of the percentage of patients responding and the extent of the responses seen was in bladder function: 75% of 16 patients with bladder symptoms improved and seven of the 11 patients with severe bladder disturbance (Kurtzke grade 3 or more) improved. Four of these seven patients had before and after cystometry and 3 showed reduced detrusor hyperreflexia. Altogether, 10 patients had a worthwhile clinical response in one or more aspects of the disease and of these, nine have so far gone on to permanent stimulation. Medium-term results (up to two years) show that, with one exception, improvement in bladder function has been maintained as long as stimulation has been continued and at least 50% of improvement in mobility has been maintained. A favourable response depends not upon the fact of stimulation but upon the type of stimulation received. This, along with other evidence, indicates that the response is not caused either by a placebo effect or by the natural fluctuation of the disease.     

The grasp reflex of the foot and related phenomena in the absence of other reflex abnormalities following cerebral commissurotomy

The grasp reflex of the foot and related pheonomena were examined in six subjects with no abnormalities of deep tendon or plantar (and related) reflexes 6 to 10 years after cerebral comissurotomy. In all subjects they were more marked on the same side as the more damaged hemisphere. These tonic phenomena seem to be facillitated by sitting and standing postures. Practical and theoretical implications of the tonic foot responses in the absence of similar phenomena of the hand are discussed.     

Cardiac parasympathetic stimulation via QRS-synchronous low-energy shocks in humans

PURPOSE: Four different three-dimensional planning techniques for localized radiotherapy of prostate cancer were compared with regard to dose homogeneity within the target volume and dose to organs at risk, dependent upon tumor stage. PATIENTS AND METHODS: Six patients with stage T1, 7 patients with stage T2 and 4 patients with stage T3 were included in this study. Four different 3D treatment plans (rotation, 4-field, 5-field and 6-field technique) were calculated for each patient. Dose was calculated with the reference point at the isocenter (100%). The planning target volume was encompassed within the 95% isodose surface. All the techniques used different shaped portal for each beam. Dose volume histograms were created and compared for the planning target volume and the organs at risk (33%, 50%, 66% volume level) in all techniques. RESULTS: The 4 different three-dimensional planning techniques revealed no differences concerning dose homogeneity within the planning target volume. The dose volume distribution at organs at risk show differences between the calculated techniques. In our study the best protection for bladder and rectum in stage T1 and T2 was achieved by the 6-field technique. A significant difference was achieved between 6-field and 4-field technique only in the 50% volume of the bladder (p = 0.034), between the 6-field and rotation technique (all volume levels) and between 5-field and rotation technique (all volume levels). In stage T1, T2 6-field and 4-field technique in 50% (p = 0.033) and 66% (p = 0.011) of the rectum volume. In stage T3 a significant difference was not observed between the 4 techniques. The best protection of head of the femur was achieved by the rotation technique. CONCLUSION: In the localized radiotherapy of prostate cancer in stage T1 or T2 the best protection for bladder and rectum was achieved by a 3D-planned conformal 6-field technique. If the seminal vesicles have been included in the target volume and in the case of large planning target volume other techniques should be taken for a better protection for organs at risk e. g. a 3D-planned 4-field technique box technique.     

Contralateral auditory stimulation alters acoustic distortion products in humans

It is now generally accepted that otoacoustic emissions (OAE) represent the only objective and non-intrusive means of functional exploration of the active micromechanical characteristics of the outer hair cells of the organ of Corti. Previous studies showed a decrease of the transiently evoked otoacoustic emissions and spontaneous otoacoustic emissions in humans, during acoustic stimulation of the contralateral ear, and attributed this effect to the medial efferent system. Such an effect has been shown on acoustic distortion product otoacoustic distortion emissions (DPOAE) in guinea pigs, but has not been investigated for DPOAEs recorded in humans, although DPOAEs represent the easiest means of exploring active micromechanical cochlear properties both in humans and in laboratory animals. The present study sought to investigate the existence and characteristics of a contralateral auditory stimulation effect on DPOAEs recorded in humans. This study shows that contralateral broad-band noise (BBN) has a suppressive effect on DPOAEs recorded from 0.5 kHz to 5 kHz. This effect is not due to air conduction, as no change in the noise floor occurred under increasing contralateral stimulation, and as no reduction in DPOAE amplitude was obtained in subjects whose contralateral ear was sealed with a plastic ear plug. Moreover, cross-over attenuation by bone transmission has been ruled out, as no change in DPOAE amplitude was recorded in the healthy ear of total unilaterally deaf patients during acoustic stimulation of the deaf ear. The effect seen was not entirely due to the acoustic reflex, as it was found and could indeed be even greater in subjects with no acoustic reflex. Results presented here show that the contralateral BBN effect is greater at low levels of ipsilateral stimulation, which leads us to discuss the involvement of both passive and active mechanisms in DPOAE generation at high stimulation levels. The contralateral BBN effect seems to be greater in mid frequency cochlear regions. There is strong evidence that the medial efferent system is involved and that afferent and efferent inputs are, at least partly, integrated at a brainstem level in order to ensure cochlear interaction. DPOAEs provide an interesting model for functional exploration of the efferent system, since they seem to be the only type of otoacoustic emission that can be recorded in both humans and in the majority of animals, and since results are obtained in the same way from both animals and humans, which allows experimental animal models very close to the human model.