A5114376128- Pharmacological Receptor Mechanisms and Effects
- Pain Mechanisms and Treatments
- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
- Phenothiazines and Benzothiazines Synthesis and Activities
- Ion Channels and Receptors
- Ion channel regulation and function
- Cholinesterase and Neurodegenerative Diseases
- Neurobiology and Insect Physiology Research
- Neuroscience and Neuropharmacology Research
- Stress Responses and Cortisol
- Nerve injury and regeneration
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Epilepsy research and treatment
- Neuroendocrine regulation and behavior
- Eicosanoids and Hypertension Pharmacology
- Pharmacogenetics and Drug Metabolism
- Musculoskeletal pain and rehabilitation
- Pharmacology and Obesity Treatment
- Nicotinic Acetylcholine Receptors Study
- Various Chemistry Research Topics
- Exercise and Physiological Responses
- Chemical synthesis and alkaloids
- N-Heterocyclic Carbenes in Organic and Inorganic Chemistry
Universidad de Granada
2016-2025
Instituto de Investigación Biosanitaria de Granada
2016-2025
Parque Tecnológico de la Salud
2009-2020
Boston Children's Hospital
2010-2018
Harvard University
2010-2018
Neurosciences Institute
2014
Boston University
2014
Sigma (sigma) receptors, initially described as a subtype of opioid are now considered unique receptors. Pharmacological studies have distinguished two types sigma termed sigma(1) and sigma(2). Of these subtypes, the receptor has been cloned in humans rodents, its amino acid sequence shows no homology with other mammalian proteins. Several psychoactive drugs show high to moderate affinity for including antipsychotic haloperidol, antidepressant fluvoxamine sertraline, psychostimulants cocaine...
Not all patients with nerve injury develop neuropathic pain. The extent of damage and age at the time are two few risk factors identified to date. In addition, preclinical studies show that pain variance is heritable. To define such further, we performed a large-scale gene profiling experiment which plotted global expression changes in rat dorsal root ganglion three peripheral models. This resulted discovery potassium channel alpha subunit KCNS1, involved neuronal excitability,...
The somatosensory nervous system is critical for the organism's ability to respond mechanical, thermal, and nociceptive stimuli. Somatosensory neurons are functionally anatomically diverse but their molecular profiles not well-defined. Here, we used transcriptional profiling analyze detailed signatures of dorsal root ganglion (DRG) sensory neurons. We two mouse reporter lines surface IB4 labeling purify three major non-overlapping classes neurons: 1) IB4+SNS-Cre/TdTomato+, 2)...
Although peripheral nerves can regenerate after injury, proximal nerve injury in humans results minimal restoration of motor function. One possible explanation for this is that injury-induced axonal growth too slow. Heat shock protein 27 (Hsp27) a regeneration-associated accelerates vitro. Here, we have shown it also do mice injury. While rapid and sensory recovery occurred sciatic crush there was little return function transection, because the delay axons reaching their target. This not due...
Inflammatory pain impacts adversely on the quality of life patients, often resulting in motor disabilities. Therefore, we studied effect peripheral inflammation induced by intraplantar administration complete Freund's adjuvant (CFA) mice a particular form voluntary locomotion, wheel running, as an index mobility impairment produced pain. The distance traveled over 1 hour free access to activity wheels decreased significantly response hind paw inflammation, peaking 24 hours after CFA...
We evaluated the role of σ1 receptors on capsaicin-induced mechanical hypersensitivity and nociceptive pain induced by punctate stimuli, using wild-type receptor knockout (σ1-KO) mice selective receptor-acting drugs. Mutation in σ1-KO was confirmed PCR analysis genomic DNA and, at protein level, [3H](+)-pentazocine binding assays. Both not treated with capsaicin showed similar responses to different intensities stimuli (0.05–8 g force), ranging from innocuous noxious, applied hind paw. This...
Epoxyeicosatrienoic acids (EETs) are cytochrome P450-epoxygenase-derived metabolites of arachidonic acid that act as endogenous signaling molecules in multiple biological systems. Here we have investigated the specific contribution 5,6-EET to transient receptor potential (TRP) channel activation nociceptor neurons and its consequence for nociceptive processing. We found that, during capsaicin-induced nociception, levels increased dorsal root ganglia (DRGs) spinal cord, is released from...
Imidazoline I2 receptors (I2-IRs) are altered in Alzheimer's disease (AD) patients and associated with analgesia. I2-IRs not structurally described, their pharmacological characterization relies on modulation by highly affine ligands. Herein, we describe the synthesis of (3-phenylcarbamoyl-3,4-dihydro-2H-pyrrol-2-yl)phosphonates endowed relevant affinities for human brain tissues. The optimal ADME pharmacokinetic profile a selected compound, 12d, secured its vivo exploration senescence...
Specific somatosensations may be processed by different subsets of primary afferents. C-fibers expressing heat-sensitive TRPV1 channels are proposed, for example, to heat but not mechanical pain detectors. To phenotype in rats the sensory function + afferents, we rapidly and selectively silenced only their activity, introducing membrane-impermeant sodium channel blocker QX-314 into these axons via pore. Using tandem mass spectrometry show that upon activation with capsaicin, accumulates...
We evaluated the effects of σ1-receptor inhibition on μ-opioid-induced mechanical antinociception and constipation. σ1-Knockout mice exhibited marked in response to several μ-opioid analgesics (fentanyl, oxycodone, morphine, buprenorphine, tramadol) at systemic (subcutaneous) doses that were inactive wild-type even unmasked antinociceptive peripheral agonist loperamide. Likewise, or local (intraplantar) treatment with selective σ1 antagonists BD-1063...
Grip strength deficit is a measure of pain-induced functional disability in rheumatic disease. We tested whether this parameter and tactile allodynia, the standard pain preclinical studies, show parallels their response to analgesics basic mechanisms. Mice with periarticular injections complete Freund's adjuvant (CFA) ankles showed immune infiltration synovial membrane alterations, together pronounced grip deficits allodynia measured von Frey hairs. However, inflammation-induced lasted...
Neuron-immune interaction in the dorsal root ganglia (DRG) plays a pivotal role neuropathic pain development after nerve injury. Sigma-1 receptor (Sig-1R) is expressed by DRG neurons but its not fully understood. We investigated effect of peripheral Sig-1R on neuroinflammation spared (sciatic) injury (SNI) mice. Nerve induced decrease NeuN staining along with nuclear eccentricity and ATF3 expression injured DRG. was present all examined, SNI this translocated to periphery soma vicinity...
Despite the myriad promising new targets and candidate analgesics recently identified in preclinical pain studies, little translation to novel medications has been generated. The phenotype humans involves complex behavioral alterations, including changes daily living activities psychological disturbances. These are not reflected by outcome measures traditionally used rodents for testing, which based on reflexes evoked sensory stimuli of different types (mechanical, thermal or chemical). do...
Sigma-1 (σ1) receptor antagonists are promising tools for neuropathic pain treatment, but it is unknown whether σ1 inhibition ameliorates the signs induced by nerve transection, in which pathophysiological mechanisms and response to drug treatment differ from other models. In addition, antagonism inflammatory through modulation of endogenous opioid system, this occurs during pain. We investigated effect on painful hypersensitivity associated with spared injury (SNI) model mice. Wild-type...