Modulation of mechanosensory vibrissal responses in the trigeminocervical complex by stimulation of the greater occipital nerve in a rat model of trigeminal neuropathic pain

Background: Stimulation of occipital or trigeminal nerves has been successfully used to treat chronic refractory neurovascular headaches such as migraine or cluster headache, and painful neuropathies. Convergence of trigeminal and occipital sensory afferents in the "trigeminocervical complex" (TCC) from cutaneous, muscular, dural, and visceral sources is a key mechanism for the input-induced central sensitization that may underlie the altered nociception. Both excitatory (glutamatergic) and inhibitory (GABAergic and glycinergic) mechanisms are involved in modulating nociception in spinal and medullary dorsal horn neurons, but the mechanisms by which nerve stimulation effects occur are unclear. This study was aimed at investigating the acute effects of electrical stimulation of the greater occipital nerve (GON) on the responses of neurons in the TCC to the mechanical stimulation of the vibrissal pad.Methods: Adult male Wistar rats were used. Neuronal recordings were obtained in laminae II-IV in the TCC in control, sham and infraorbital chronic constriction injury (CCI-IoN) animals. GON was isolated and electrically stimulated. Responses to stimulation of vibrissae by brief air pulses were analyzed before and after GON stimulation. In order to understand the role of neurotransmitters involved, specific receptor blockers of NMDA (AP-5), GABAA (bicuculline, Bic) and Glycine (strychnine, Str) were locally applied.Results: GON stimulation produced a facilitation of the response to light facial mechanical stimuli in controls, and an inhibition in CCI-IoN cases. AP-5 reduced responses to GON and vibrissal stimulation and blocked the facilitation of GON on vibrissal responses found in controls. The application of Bic or Str reduced significantly the facilitatory effect of GON stimulation on the response to vibrissal stimulation in controls. However, the opposite effect was found when GABAergic or Glycinergic transmission was prevented in CCI-IoN cases.Conclusions: GON stimulation modulates the responses of TCC neurons to light mechanical input from the face in opposite directions in controls and under CCI-IoN. This modulation is mediated by GABAergic and Glycinergic mechanisms. These results will help to elucidate the neural mechanisms underlying the effectiveness of nerve stimulation in controlling painful craniofacial disorders, and may be instrumental for identifying new therapeutic targets for their prevention and treatment.

A novel Ca2+-feedback mechanism extends the operating range of mammalian rods to brighter light

Sensory cells adjust their sensitivity to incoming signals, such as odor or light, in response to changes in background stimulation, thereby extending the range over which they operate. For instance, rod photoreceptors are extremely sensitive in darkness, so that they are able to detect individual photons, but remain responsive to visual stimuli under conditions of bright ambient light, which would be expected to saturate their response given the high gain of the rod transduction cascade in darkness. These photoreceptors regulate their sensitivity to light rapidly and reversibly in response to changes in ambient illumination, thereby avoiding saturation. Calcium ions (Ca2+) play a major role in mediating the rapid, subsecond adaptation to light, and the Ca2+-binding proteins GCAP1 and GCAP2 (or guanylyl cyclase–activating proteins [GCAPs]) have been identified as important mediators of the photoreceptor response to changes in intracellular Ca2+. However, mouse rods lacking both GCAP1 and GCAP2 (GCAP−/−) still show substantial light adaptation. Here, we determined the Ca2+ dependency of this residual light adaptation and, by combining pharmacological, genetic, and electrophysiological tools, showed that an unknown Ca2+-dependent mechanism contributes to light adaptation in GCAP−/− mouse rods. We found that mimicking the light-induced decrease in intracellular [Ca2+] accelerated recovery of the response to visual stimuli and caused a fourfold decrease of sensitivity in GCAP−/− rods. About half of this Ca2+-dependent regulation of sensitivity could be attributed to the recoverin-mediated pathway, whereas half of it was caused by the unknown mechanism. Furthermore, our data demonstrate that the feedback mechanisms regulating the sensitivity of mammalian rods on the second and subsecond time scales are all Ca2+ dependent and that, unlike salamander rods, Ca2+-independent background-induced acceleration of flash response kinetics is rather weak in mouse rods.

Case Series on Variable Presentation of Ligamentum Flavum Stimulation Following Percutaneous Cylindrical Spinal Cord Stimulator Lead Implants

Background: Stimulation-evoked discomfort secondary to ligamentum flavum stimulation (LFS) is a technological limitation of percutaneous spinal cord stimulator (SCS) lead implants. There is a paucity of literature describing the clinical presentation and time periods at which this side effect may present following insertion of cylindrical lead(s). Objective: To describe a series of 5 patients who presented at varying time periods after SCS lead placement with LFS. Study Design: Retrospective case series. Methods: We performed a chart review of online medical records of patients with symptoms consistent with LFS at an academic interventional pain clinic identified over 7 consecutive years (2006 - 2013). Results: LFS most frequently presented within months of implantation of cylindrical leads. One patient complained of LFS during the temporary trial while another developed LFS after lead revision. All patients were successfully treated when paddle electrodes replaced percutaneous cylindrical leads. Conclusion: LFS may present as a barrier to successful SCS treatment. Clinicians placing percutaneous SCS leads should be aware of the variable time course of LFS presentation. Paddle style electrodes seem to offer an enduring solution to LFS so that patients may continue to benefit from SCS therapy. Key words: Percutaneous electrodes, cylindrical electrode, paddle electrodes, ligamentum flavum stimulation, unwanted stimulation

Olfactory Cortical Adaptation Facilitates Detection of Odors Against Background

Detection and discrimination of odors generally, if not always, occurs against an odorous background. On any given inhalation, olfactory receptor neurons will be activated by features of both the target odorant and features of background stimuli. To identify a target odorant against a background therefore, the olfactory system must be capable of grouping a subset of features into an odor object distinct from the background. Our previous work has suggested that rapid homosynaptic depression of afferents to the anterior piriform cortex (aPCX) contributes to both cortical odor adaptation to prolonged stimulation and habituation of simple odor-evoked behaviors. We hypothesize here that this process may also contribute to figure-ground separation of a target odorant from background stimulation. Single-unit recordings were made from both mitral/tufted cells and aPCX neurons in urethan-anesthetized rats and mice. Single-unit responses to odorant stimuli and their binary mixtures were determined. One of the odorants was randomly selected as the background and presented for 50 s. Forty seconds after the onset of the background stimulus, the second target odorant was presented, producing a binary mixture. The results suggest that mitral/tufted cells continue to respond to the background odorant and, when the target odorant is presented, had response magnitudes similar to that evoked by the binary mixture. In contrast, aPCX neurons filter out the background stimulus while maintaining responses to the target stimulus. Thus the aPCX acts as a filter driven most strongly by changing stimuli, providing a potential mechanism for olfactory figure-ground separation and selective reading of olfactory bulb output.

Gut perception in humans is modulated by interacting gut stimuli

Digestive symptoms depend on multiple interacting gut stimuli, but integration of visceral afferent traffic is poorly understood. Our aim was to elucidate the contribution of simultaneous intestinal stimuli to conscious perception. In 17 healthy subjects, we performed stimulus-response trials of jejunal distensions (1-min duration at 5-min intervals in 8-ml increments) either alone or with a background electrical stimulus, and stimulus-response trials of electrical stimuli (1-min duration at 5-min intervals in 6-mA steps) either alone or with a background intestinal distension. The four stimulus-response trials were performed concomitantly applying the different types of stimuli in random order. Perception was measured on a scale of 0 to 6. Background stimulation markedly increased perception of test stimuli, reducing tolerance from 44 ± 3 to 32 ± 3 ml and from 67 ± 6 to 33 ± 4 mA ( P < 0.05 for both). However, whereas jejunal distensions below the perception threshold did not modify perception of the background stimulus (4 ± 1% change; not significant), unperceived electrical stimuli exerted a sensitizing effect and increased perception of the background distension up to uncomfortable levels (111 ± 40% increment; P < 0.05). In conclusion, activation of different pools of jejunal afferents produces summative effects on perception, and this sensitizing effect can be exerted by unperceived stimulation of mechanoinsensitive jejunal afferents.

Effects of Background Stimulation upon Eye-Movement Information

To investigate the effects of background stimulation upon eye-movement information (EMI), the perceived deceleration of the target motion during pursuit eye movement (Aubert-Fleishl paradox) was analyzed. In the experiment, a striped pattern was used as a background stimulus with various brightness contrasts and spatial frequencies for serially manipulating the attributions of the background stimulus. Analysis showed that the retinal-image motion of the background stimulus (optic flow) affected eye-movement information and that the effects of optic flow became stronger when high contrast and low spatial frequency stripes were presented as the background stimulus. In conclusion, optic flow is one source of eye-movement information in determining real object motion, and the effectiveness of optic flow depends on the attributes of the background stimulus.