Overall, there was statistically a significant increase (P=0.01) in the expression level of cartilage-specific genes in cultures with 0.01 µM BIO (enhancing effects). These upregulations appeared to be mediated through the Wnt pathway evident from the significant upregulation of selleck chemical T-cell factor and beta-catenin molecules (P=0.01). Inhibitors,research,lifescience,medical Conclusion: Taken together, BIO at 0.01 µM could accelerate and enhance in vitro chondrogenesis of mouse marrow-derived MSCs. Keywords: Mesenchymal stem cells, Mouse, 6-bromoindirubin-3-oxim Introduction The treatment of injuries

to the hyaline cartilage is considered a challenge in the field of orthopedic surgery. This is because of very limited repair capacity of the hyaline cartilage. Chondrocytes in the mature cartilage have lost their ability to undergo proliferation and are, hence, unable to participate in the repair process. Furthermore, the cartilage is described Inhibitors,research,lifescience,medical as an avascular tissue. Inhibitors,research,lifescience,medical The existence of blood vessels is necessary for triggering an inflammatory response, which brings repair cells, including monocytes and macrophages, to the injury site. Often hyaline cartilage defects fill with fibrocartilage,

which is not biomechanically suitable for weight-bearing.1,2 Current therapies used in the clinic to reconstruct the cartilage tissue include marrow stimulation techniques such as microfracture, osteochondral mosaicplasty, Inhibitors,research,lifescience,medical and cell-based treatments.3-5 There are two types of cell-based treatments for cartilage defects: autologous chondrocyte implantation (ACI) and mesenchymal stem cell (MSC)-based therapy.6 ACI involves the preparation of chondrocytes from an intact region of the cartilage and their culture-expansion and transplantation by surgery. This technique involves a two-step surgical procedure: one for collecting the tissue and the other for the transplantation of the cells. Moreover, Inhibitors,research,lifescience,medical obtaining a sufficient number of chondrocytes from the tissue biopsies is challenging;

medroxyprogesterone therefore, in vitro expansion of the cells is inevitable. It has been reported that chondrocytes expanded in culture gradually undergo dedifferentiation and loose morphological features as well as specialized functions.7 Considering the drawbacks associated with chondrocytes and in the search for better cell source, MSCs have been found a suitable candidate for application in cartilage regeneration thanks to their extensive self-renewal property and chondrogenic differentiation capacity.8,9 MSCs were first described by Fridenstein et al.10,11 from bone marrow tissue as colonogenic fibroblastic cells capable of producing bone and cartilage-like tissues in culture.

This was addressed in a second fitness test: Each participant had to perform a three-minute ramp protocol on a rowing ergometer starting at 25 watts. Strain was increased by 25-watt steps to a minimum of 75

watts and a maximum of 125 watts. Stroke frequency had to be kept constant at between 30-40/min. As the seat of the custom-made rowing Vemurafenib datasheet machine was not movable, all force had to be recruited from the upper part of the body. Between the cycling and the rowing ergometry tests, all participants were allowed to recover for at least two hours. Full recovery was verified by repeated lactate measurements until two consecutive measurements had returned to the individual’s baseline values. Ergospirometry Ergospirometric measurements Inhibitors,research,lifescience,medical were performed with a mobile breath-by-breath ergospirometry device (Cortex Metamax 3 B™, Cortex Biophysik, Leipzig, Germany), combined with a chest-belt heart rate meter (Polar T 41™, Polar Electro, Inhibitors,research,lifescience,medical Büttelborn, Germany) during the endurance tests.

We recorded respiratory rate, respiratory minute volume, oxygen consumption, carbon dioxide production and HR. All parameters were transmitted to a Windows™ based PC and recorded using MetaSoft 3.3™ software (Cortex Biophysik, Leipzig, Germany). As PWC170 is a validated, standard, cycling-based parameter of physical fitness, we aimed to determine a corresponding fitness parameter evaluated during rowing exercises. Therefore, correlations for ergospirometric parameters measured Inhibitors,research,lifescience,medical during rowing with Inhibitors,research,lifescience,medical the individual PWC170 were calculated. Part II: External chest compression Two days after part I, the participants performed two nine-minute sequences of ECC. We chose nine-minute sequences because this is approximately the average time that a first responder has to give ECC during out-of-hospital resuscitation prior to the arrival of professional healthcare providers at the scene [15,16]. Using a computer-generated randomization list, participants were randomly assigned to Inhibitors,research,lifescience,medical start ECC with a CVR of either 15:2 or 30:2, followed by a CVR of

30:2 or 15:2 in a crossover manner. Between the two ECC sequences, all participants were allowed to recover for at least 90 minutes. Full recovery was verified by repeated lactate measurements until two consecutive measurements had returned to the individual’s baseline values. ECC was performed on a standard ALS manikin (ResusciAnne™, Thiamine-diphosphate kinase Laerdal Medical, Stavanger, Norway) placed on the floor with a linear force-depth relationship (32.5 kg 38 mm, 44 kg 51 mm, see Figure ​Figure1).1). The quality of the ECC, determined by the compression depth and rate was measured and recorded by a PC-based automated skill reporting system (SkillMaster™ Reporting System, Laerdal Medical, Stavanger, Norway). In a brief pre-trial test, all participants were initially reminded to use the correct compression site (centre of the chest), rate (100 min-1) and depth (4-5 cm), but no corrective feedback was given during the course of the trial.

The mean weight was similar and remained between the 25th and 50th percentile for treated boys with both protocols at 9, 12 and 15 years. In the Naples control group, body weight was consistently 25% higher compared to the treated group. In the Toronto control group, the weight was the same as the treated group at 9 years, increased compared to the treated group at 12 years and was less than the treated group at 15 years. Height was reduced Inhibitors,research,lifescience,medical for treated boys compared to controls in both protocols for 9 and 12 years. There was greater growth

suppression in the Toronto protocol compared to the Naples protocol at 12 and 15 years. Pulmonary and cardiac function for the 2 protocols were not presented. Members of the Canadian Pediatric Neuromuscular Group were surveyed to determine the current care of pediatric DMD patients across Canada (27). Deflazacort (0.9 mg/kg/d) was the corticosteroid prescribed at all centers. Two of the centers occasionally prescribe

selleck screening library prednisone (0.75 mg/kg/d) (27). The care for individuals Inhibitors,research,lifescience,medical with DMD across Canada is relatively consistent and includes multidisciplinary teams, continuation of deflazacort treatment after loss of independent ambulation, routine calcium and vitamin D supplementation, and the use of night splints to maintain ankle dorsiflexion. Inhibitors,research,lifescience,medical All sites also include routine surveillance of pulmonary function, cardiac function (electrocardiogram and Inhibitors,research,lifescience,medical echocardiogram) and bone density scans. The standard of care is consistent with the recommendations from Bushby et al. (1, 2) regarding management of DMD. Five articles have been published regarding Canadian clinical data evaluating the impact of deflazacort in DMD (8-12, 18). One paper has been submitted for publication (28). One Canadian paper is not included in this review because the data included boys with DMD Inhibitors,research,lifescience,medical treated with both prednisone and deflazacort (29). Montreal and Toronto are the two centers in Canada that have published their experience regarding the long term benefits of deflazacort in DMD (8-12, 18, 28). Houde et al. (11) published a retrospective these review of 79 patients with DMD (Table 1).

Biggar et al. (10) published an open label study of 74 patients with DMD (Table 1). Both cohorts of patients were started at a dose of 0.9 mg/kg/d of deflazacort, vitamin D (400 IU [11] or 1000 IU [10]) and elemental calcium (250 mg tid [11] or 750 mg daily [10]). The Toronto cohort recommended calcium and vitamin D to patients not treated with deflazacort (10). Table 1. General characteristics. Muscle strength Muscle strength was preserved in both cohorts comparing treated patients to the control group. Muscle strength was measured differently at the two centers. In Montreal, they graded manual muscle testing according to the Medical Research Council Scale in 34 muscles. Scores were cumulated and converted to a percentage of normal.

Finally, progress in the genetics of human epilepsies has e had important consequences for clinical practice. Spell cific molecular diagnosis is now possible in symptomatic e individuals for several diseases, some of which have poor prognoses. Predictive diagnosis in presymptomatic indie viduals is also possible, although it does pose ethical

problems. From a pharmacological point of view, Inhibitors,research,lifescience,medical these recent genetic discoveries should help understand the response (or resistance) of some epileptic syndromes to ri treatment and the adverse effects sometimes observed with antiepileptic drugs, and generate new antiepileptic drugs. Selected abbreviations and acronyms ADNFLE autosomal dominant nocturnal frontal lobe epilepsy BFNC benign familial neonatal convulsions GEFS+ generalized Inhibitors,research,lifescience,medical epilepsy with febrile seizures-plus nAChR nicotinic acetylcholine receptor PME progressive myoclonus epilepsy Notes We wish to thank Dr Merle Ruberg for critical reading of the manuscript.
The “classical”

dopamine (DA) hypothesis of schizophrenia proposed that hyperactivity of DA transmission is responsible for the positive symptoms (hallucinations, delusions) observed in this Inhibitors,research,lifescience,medical disorder.1 This hypothesis was supported by the correlation between clinical doses of antipsychotic drugs and their potency for blocking DA D2 receptors,2-3 and by the psychotogenic effects of DA-enhancing drugs (for reviews, see references 4 and Inhibitors,research,lifescience,medical 5). These critical pharmacological observations suggested, but did not establish, a dysregulation Inhibitors,research,lifescience,medical of DA systems in schizophrenia. On the other hand, negative and cognitive symptoms are generally resistant to treatment by antipsychotic drugs. Impairment in higher cognitive functions, such as working memory, is one of the most, enduring

symptoms of schizophrenia and a strong predictor of poor clinical outcome.6 Functional brain-imaging studies suggested that these symptoms arc associated enough with a dysfunction of the prefrontal cortex (PFC).7-9 Studies in nonhuman primates demonstrated that deficit in DA transmission in the PFC and lack of stimulation of D1 selleck chemicals receptors (the main DA receptor subtype in the PFC) induce cognitive impairments reminiscent of those observed in patients with schizophrenia.10 Together, these observations suggest that a deficit in DA transmission at D-, receptors in the PFC might be implicated in the cognitive impairments presented by these patients.

15,16 PROG has a substantial treatment

window and can be given up to 24 hours after injury and still show beneficial effects in animal and clinical TBI.5,17 Importantly, it has been shown to produce significant sparing of cognitive, sensory, and spatial learning AZD0530 clinical trial performance in mature and aged rats following bilateral brain injuries.18 A number of reviews discuss these data and highlight the fact that PROG and its key metabolites play a critical role in both normal development and repair of the CNS after injury (see Figure 1 for a diagram Inhibitors,research,lifescience,medical of the metabolic pathways of this hormone).19-25 Figure 1. Steps in the biosynthesis of progesterone and some of its metabolites. Thus far much of our group’s research on PROG Inhibitors,research,lifescience,medical and its metabolites has focused on the treatment of TBI. 8,14,26-29 This line of research originated when we found that following bilateral contusion Inhibitors,research,lifescience,medical injury to the medial frontal cortex (MFC) in young adult, male and female rats, 3 to 5 days of post-injury treatment, with PROG significantly reduced

cerebral edema and improved spatial learning and sensory performance compared with controls given vehicle alone.30,31 Progesterone tested successfully in two phase II clinical trials Inhibitors,research,lifescience,medical The first successful clinical trial for the treatment of TBI in more than 30

years of Inhibitors,research,lifescience,medical research was published in 2007.17 This NINDS-sponsored, Phase Ha single-center clinical trial for PROG in the treatment of moderate-to-severe adult TBI found that the mortality rate among patients given PROG intravenously for 3 days post-injury was less than half that, of controls (13.6% versus 30.4%). Thirty-day functional outcomes for moderately injured patients in the PROG group were significantly Dichloromethane dehalogenase better than those for the placebo group. An NIH-appointed Data Safety Monitoring Board found no serious adverse events attributable to PROG treatment. A second independent, randomized doubleblind study from China tested PROG in 159 patients with severe TBI given a course of intramuscular injections for 5 days. The investigators reported similar beneficial outcomes on morbidity and mortality at both 30 days and 6 months after injury, again without any serious adverse events caused by the treatment.

Many studies on the therapeutic potential of such microRNA engineering have shown promising results. For instance, intratumoral as well as systemic delivery of synthetic let-7 microRNA, whose level is downregulated in lung cancer, was found to cause tumor regression in a mouse model of lung

cancer (68), and disease progression in a mouse model of hepatocellular carcinoma was found to be halted by systemic delivery of adeno-associated viruses engineered to express miR-26a (69). MicroRNAs and esophageal carcinoma Guo and colleagues were the first to report microRNA expression profiles in esophageal cancer, in 2008. Microarrays were used to profile 435 microRNAs in RNA extracted Inhibitors,research,lifescience,medical from fresh-frozen specimens of 31 pairs of ESCC and corresponding

adjacent normal esophageal tissues (70). One-hundred-ninety-one microRNAs were considered Inhibitors,research,lifescience,medical detectable, and their expression profiles could be used to discern cancerous from normal tissue with >90% accuracy. MicroRNAs miR-25, miR-424 and miR-151 showed upregulation, and miR-100, miR-99a, miR-29c, and miR-140* showed reduction in cancerous Inhibitors,research,lifescience,medical tissue. Higher expression of miR-103 and miR-107, known to affect metastatic potential of cancers by downregulating Dicer levels (58), was associated with poor prognosis. In a study that was published in the same year, Feber, et al., used RNA from fresh-frozen tissue samples from ten cases each of EAC and ESCC, and five cases of BE, to assay the expression of 328 human microRNAs (71). Compared to normal esophagus, miR-203 and miR-205 were expressed two-to-ten-fold less in all three diseases, whereas miR-21 levels were three-to-five-fold Inhibitors,research,lifescience,medical higher. Reduced levels of miR-203 and

miR-205 were also observed in columnar epithelium compared to normal squamous epithelium in a study that examined 377 microRNAs in 16 individuals using microarrays (72). Levels of miR-205 were also found to be lower in BE mucosa compared to normal adjacent epithelium as well as to neosquamous epitheium generated following ablation of Barrett’s epithelium with Argon plasma coagulation in a study involving nine patients (73). MicroRNA miR-21 was Inhibitors,research,lifescience,medical also identified as overexpressed in a study that used RT-PCR to examine 20 cases of ESCC and seven ESCC cell-lines, and in two other studies, and it has been shown to be only an oncogene that promoted cell transformation by targeting transcripts for the Programmed cell death 4 (PDCD4) protein (72), (74)-(76). Though some microRNAs, such as miR-21, miR-100, miR-203 and miR-205, were identified as being affected in esophageal carcinoma in more than one of the aforementioned studies, many, like miR-143, miR-145 and miR-215, whose levels are find more increased in EAC as well as BE (74), were not. Characteristics of patient populations and RNA quantification technologies, and differences in sample-sizes and data analyses are believed to be responsible for this, a theme that occurs recurrently in such biomarker discovery work.

2006). Intrathecal administration of FGF2 after moderate or severe SCI in rats was associated with earlier and more pronounced hind limb movements and coordination compared to control group (Rabchevsky et al. 1999, 2000; Kasai et al. 2010). These remarkable effects of FGF2 have, therefore, led to its use in different treatment strategies for neural injury. In this study, the authors reported using subcutaneous FGF2 injection as early as 30 min after Tyrphostin AG-1478 cost injury and up to 2 weeks. This method was unique up to our knowledge in treatment of similar conditions because it has been shown that with systemic administration, FGF2 will exhibit unequal distribution to the body Inhibitors,research,lifescience,medical organs due to its heparin-binding

domain (Epstein et al. 2001), and will be exposed to rapid tissue clearance (Kang et al. 2013). More importantly, it has also been reported that blood-spinal cord

barrier Inhibitors,research,lifescience,medical (BSB) has a very limited permeability to FGF2 (Epstein et al. 2001; Kang et al. 2010a,b2010b). Therefore, previous studies, including both cited references by the current authors for FGF2 application in rodents with SCI (Lee et al. 1999; Rabchevsky et al. 1999), have administered FGF2 either intrathecally or directly into the site of SCI. Following brain injury, however, some studies have shown that the disrupted blood–brain barrier (BBB) becomes more permeable for some hours Inhibitors,research,lifescience,medical to days, and this window can be used for systemic infusion of FGF2 with promising results (Liu et al. 2006). Whether this time frame also represents a therapeutic window for FGF2 administration following SCI in this study is not known. It is also important to emphasize that a hemisection model is used in this study. Although the majority of spinal cord injuries in human are contusions rather than transections, in experimental spinal cord research, Inhibitors,research,lifescience,medical a transection model is preferred, because crossover through the uninjured side, is a well-known phenomenon (Cowley et al. 2008; Oudega and

Inhibitors,research,lifescience,medical Perez 2012). Transection, however, leads to animal morbidity and loss, and many times, a hemisection model is used and the crossover effect is partially compensated by having controls and shams. However, having controls and shams is not an absolute compensation and transection models are preferred. In summary, this collection of pilot studies has focused on a number of important parameters crucial for MTMR9 experimental animal spinal cord research. The overall results at first sight look promising. Some of the results have been studied earlier or at least in other species but the endpoints are valid and interesting. Nevertheless, the number of animals in each of these five pilot studies is low. Not specific for this study, we should remember that many of the animal studies with promising results are not reproducible (Button et al. 2013), the hemisection model is not optimal (Cowley et al. 2008), mice have an extreme ability for functional potentiation of the uninjured neurons (Steward et al.

While the past few decades have aided its development, the upcoming decades will inform its refinement and take advantage of its multifunctional properties. Indeed, subconvulsive TMS and convulsive MST have been found to have beneficial neurocognitive effects, which substantiate their continued development and employment in the neuropsychiatric arena. Acknowledgments This review was funded in part by NIH grants K23 MH087739 and K01 AG031912, and the Stanley Medical Research Foundation. Selected abbreviations

and acronyms AD Alzheimer’s disease LTD long-term depression LTP long-term potentiation MEP motor evoked potential MST magnetic seizure therapy PAS paired associate stimulation Inhibitors,research,lifescience,medical PD Parkinson’s disease RT reaction time rTMS repetitive transcranial magnetic stimulation SD sleep deprivation TMS transcranial magnetic stimulation
Plasticity of the human brain has been extensively studied during development. Children who had undergone hemispherectomy for intractable epilepsy and who showed a remarkable Inhibitors,research,lifescience,medical recovery of motor function or language probably represent the most illustrative example of brain plasticity and its correlation with recovery from a neurological deficit. On the other hand, plasticity of the adult brain tends to remain an uncommon click here concept; plasticity does go somewhat against the traditional phrenologic approach Inhibitors,research,lifescience,medical to the human brain. Broca

gave strong support to localizationist concepts of brain function when he correlated, in 1861, a lesion of the left temporal lobe with aphasia. Little room was available for the notion of brain plasticity during that period, Inhibitors,research,lifescience,medical despite significant reports of clinical recovery from neurological deficits. However, evidence for plasticity of the adult brain has more recently (in the last 30 Inhibitors,research,lifescience,medical years) been recognized. It is now accepted that recovery after a brain lesion can continue for years. Hemispherectomy, experiments with sensory

substitution, muscle transposition after motor deficit, and facial paralysis which recovered after VII-XII cranial anastomosis strongly pleaded in favor of a certain capacity for plasticity of the adult human brain. Moreover, the daily clinical practice of neurologists Urease provides strong arguments for capacities of reorganization of the adult human brain after a lesion. For example, recovery of function can represent an argument for the diagnosis of stroke in patients who have undergone a focal neurological deficit of abrupt onset.1-6 Stroke greatly differs from neurodegenerative diseases as it is a consequence of a single acute focal lesion of the brain. A heavy burden for our society, it results in a large number of deaths and prolonged neurological deficits in many patients. Recovery from stroke represents a major issue for these patients, and is a good illustration of brain plasticity. Stroke occurs more frequently in aged people; more than 50% of strokes involve people over 85.

The “chip” term emphasizes the capacity to mass-produce the sensor elements in a way similar to those used by the microelectronics industry that ultimately leads to high performance at reduced cost. The same sensor platform has the capacity to measure both soluble analytes using bead microreactors (Danusertib Figure 1B)17–24 as well as cell counting, typing, and differentiation using membrane microstructures (Figure 1C).25–27 Figure 1. (A) P-BNCs

are programmed to measure medically relevant species in complex biological samples through the employment of three-dimensional “nano-nets” composed of agarose strands supported within 280 μm Inhibitors,research,lifescience,medical bead “micro-sponges,” … These two distinct types of assay platforms are packaged with in a disposable, single-use P-BNC sensor lab card (Figure 2). The lab card — with Inhibitors,research,lifescience,medical built-in incipient-stabilized detection reagents, fluid mixing and partitioning compartments, and a sample-loading dock and self-contained

bio-waste compartment — is inserted in the light-emitting diode/charge-coupled, device-equipped, mechano-optical analyzer to complete entire assay Inhibitors,research,lifescience,medical sequences in an automated manner. The toaster-size portable analyzer serves as a universal-interface portable smart device that includes an embedded PC. It also provides for mechanical, optical, and software capabilities operated through a user interface that functions upon insertion of the lab card and concludes with an easy-to-interpret liquid crystal display readout of the test result. Figure 2. From macro to nano. (A) In the P-BNC system, interface with the human user occurs via a portable, self-contained analyzer that (A/B) processes a compact, modular, single-use/disposable lab card. (C) The lab card

Inhibitors,research,lifescience,medical houses the diagnostic core of the P-BNC, … Compared to gold standard methods such as enzyme-linked immunoassay (ELISA), P-BNCs exhibit assay times in minutes instead of hours, a limit of detection (LOD) 2 or more orders of magnitude lower, and a proven capacity Inhibitors,research,lifescience,medical to multiplex 10 or more concurrent analytes with appropriate internal controls and calibrators. The first strong analytical performance of the P-BNCs may be attributed to the porous nature of its bead sensors, the active transport mode of delivery of the sample and detection reagents, and the highly stringent washes associated with this microfluidic approach. Like ELISA, the bead-based P-BNCs complete 2-site immunometric as well as competitive immunoassays. Unlike ELISA, which limits the diffusion-mediated antigen-antibody (Ag-Ab) binding to a 2-dimensional planar surface at the bottom of the well, P-BNCs provide a roughly 1000-fold to 10,000-fold increase in surface area on the 3-dimensional (3D) bead sensor. This 3D reactor allows for significantly increased contact area and on-off-on again, higher avidity Ag-Ab interactions.

2000). In contrast to most other main nerve trunks, the first and second trigeminal branches are purely sensory, and the motor (masticatory) component of the third Selleckchem LBH589 branch is distinctly separated from the sensory component by a thick perineurial sheath, from the trigeminal root to the proximal part of the branch. Moreover, there are several human pain conditions that affect specifically the trigeminal nerves and a differential

Inhibitors,research,lifescience,medical sensitivity to certain drugs in neuropathic pain in the trigeminal versus other territories has been observed (Idanpaan-Heikkila and Guilbaud 1999; Watson 2004). It is therefore valuable to develop specific animal models for the orofacial area. This review presents an overview of the rodent models developed for the trigeminal area over the last 20 years, with the emphasis on behavioral tests. To date, most reviews have overviewed the mechanistic

components of trigeminal Inhibitors,research,lifescience,medical pain but none have focused specifically on the various behavioral testing methods available in rodents. For reviews which specifically elucidate the mechanisms of orofacial pain, see for example Sessle (2005), Inhibitors,research,lifescience,medical Hargreaves (2011), Takeda et al. (2011), Iwata et al. (2011). The scope of this review will span basic research on the rodent skin and mucosa, and muscular and articular sensory territories of the trigeminal Inhibitors,research,lifescience,medical nerve that has been published in the last few decades. For reasons of simplicity, and because these topics have already been broadly discussed in the literature, models that involve specific target organs such as teeth, the eye, and salivary glands will be omitted. Useful reviews and reports are available on dental pain (Cooper

and Desjardins 2010; Tarsa et al. 2010; Hargreaves 2011), eye pain (Tashiro et al. 2010; Marquart 2011), and salivary gland pain (Ogawa et al. 2003). Cancer pain has certain inflammatory components and sometimes some neuropathic pain aspects (Mantyh et al. 2002; Benoliel et al. Inhibitors,research,lifescience,medical 2007). The behavioral evaluation methods used in animal models of orofacial cancer pain are similar to those used in other orofacial pain models (Nagamine et al. 2006; Ono et al. 2009; Harano Rolziracetam et al. 2010) and this topic will also not be explored in this review. Finally, chronic primary headaches, including migraines, fall into craniofacial disorders but are not usually considered “orofacial” conditions1 (Zakrzewska 2009) and thus will not be discussed. Of particular interest will be models of TN, TMD, and facial muscle pain and other models of cutaneous nociception in rodent orofacial pain. While several recent reviews have summarized some of the techniques used to induce neuropathic or inflammatory pain in the facial region (Khan and Hargreaves 2010; Iwata et al.