kaolinite and Arthritis

Oenothera rosea (Onagraceae), commonly known as "hierba del golpe" in Mexico, is an herbaceous plant widely used in Mexican traditional medicine for the treatment of pain and inflammation.. The aim of this study was to assess the effect of extracts and compounds isolated from O. rosea in kaolin-carrageenan induced arthritis.. Hydroalcoholic extract from aerial parts of O. rosea was obtained and chemically separated in order to obtain OrEA and isolated compounds using column chromatography, HPLC, UPLC and NMR analysis. O. rosea extract and derivatives were tested on the kaolin/carrageenan (K/C) induced arthritis model on ICR mice. Knee inflammation and paw withdrawal threshold were assessed following intraarticular administration of kaolin and carrageenan (4% and 2%, respectively) and subsequent oral administration of O. rosea. TNF-α, IL-1β, IL-6 and IL-10 levels from synovial capsule were measured using ELISA kits. NF-κB activity was also measured using the RAWBlue™ cell line. Finally, spleen and lungs were dissected to investigate body index.. Oral administration of the O. rosea ethyl acetate fraction (25, 50 and 100 mg/kg) and isolated compounds (2 mg/kg) reduced the edema induced by kaolin/carrageenan, similar to the effect of methotrexate (1 mg/kg). Hyperalgesia but not allodynia was observed during this experiment. O. rosea derivatives reduced this behavior. The quantification of cytokines showed a reduction in TNF-α, IL-1β and IL-6, as well as an increase of IL-10. NF-κB production was also reduced by administering O. rosea derivatives. Chemical analysis of O. rosea derivatives showed that the major compounds present in the ethyl acetate fraction were phenolic compounds. Gallic acid, quercetin glucoside and quercetin rhamnoside were separated and identified by UPLC-UV-MS, and myricetin glycoside and tamarixetin glucoside using. O. rosea produces different phenolic compounds capable of reducing the inflammation and secondary mechanical hyperalgesia produced by K/C administration. They also reduced proinflammatory cytokines and increased anti-inflammatory cytokines. Finally, NF-κB modulation was reduced by the administration of O. rosea. Therefore, O. rosea could be considered of interest in inflammatory and painful diseases.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Arthritis; Carrageenan; Cell Line; Cytokines; Disease Models, Animal; Female; Hyperalgesia; Kaolin; Mice, Inbred ICR; NF-kappa B; Oenothera; Phenols; Phytochemicals; Plant Components, Aerial; Plant Extracts; Synovial Membrane

Neuroplastic changes in the amygdala account for emotional-affective aspects of pain and involve neuropeptides such as calcitonin gene-related peptide and corticotropin-releasing factor. Another neuropeptide system, central arginine vasopressin, has been implicated in neuropsychiatric disorders, but its role in pain-related emotional expression and neuroplasticity remains to be determined. Here, we tested the hypothesis that arginine vasopressin in the amygdala contributes to pain-related emotional-affective responses, using stereotaxic applications of arginine vasopressin and antagonists for G-protein coupled vasopressin V1A and oxytocin receptors in adult male Sprague-Dawley rats. In normal animals, arginine vasopressin increased audible and ultrasonic vocalizations and anxiety-like behavior (decreased open-arm preference in the elevated plus maze). The facilitatory effects were blocked by a selective V1A antagonist (SR 49059, Relcovaptan) but not by an oxytocin receptor antagonist (L-371,257). L-371,257 had some facilitatory effects on vocalizations. Arginine vasopressin had no effect in arthritic rats (kaolin/carrageenan knee joint pain model). SR 49059 inhibited vocalizations and anxiety-like behavior (elevated plus maze) in arthritic, but not normal, rats and conveyed anxiolytic properties to arginine vasopressin. Arginine vasopressin, SR 49059, and L-371,257 had no significant effects on spinal reflexes. We interpret the data to suggest that arginine vasopressin through V1A in the amygdala contributes to emotional-affective aspects of pain (arthritis model), whereas oxytocin receptors may mediate some inhibitory effects of the vasopressin system.

Topics: Amygdala; Animals; Arthritis; Benzoxazines; Carrageenan; Disease Models, Animal; Hormone Antagonists; Indoles; Kaolin; Male; Maze Learning; Microdialysis; Pain; Piperidines; Pyrrolidines; Rats; Rats, Sprague-Dawley; Receptors, Oxytocin; Receptors, Vasopressin; Reflex; Vocalization, Animal

intra-articular co-injection of kaolin with carrageenan (CGN) in rodents is widely used as an experimental model of arthritis. However, the ability of kaolin to cause arthritis and related immune responses when administered alone is unclear. We evaluated the contribution of prostanoids and sensory C-fibres (and their neuropeptide substance P) to kaolin-induced inflammation in the rat knee.. Wistar rats, 8-10 weeks old, received an intra-articular injection of kaolin (1-10 μg/joint) or saline into the knee joint. Knee inflammation, proinflammatory cytokines, pain behaviour and secondary tactile allodynia were assessed over 5 h, when synovial leukocyte counts, histopathological changes and proinflammatory cytokine levels were evaluated.. The intra-articular injection of kaolin caused a dose- and time-dependent knee swelling and impairment of motion that were associated with secondary tactile allodynia, elevated concentrations of IL-1β, IL-6 and TNFα, leukocyte infiltration, and histopathological changes in the ipsilateral hindpaw. The neurokinin-1 (NK1) receptor antagonist SR140333 or neonatal treatment with capsaicin markedly reduced the inflammatory parameters, cytokines and allodynia but failed to significantly inhibit the impaired motion. The cyclo-oxygenase inhibitor indomethacin partially inhibited knee oedema and allodynia but did not affect the leukocyte influx, myeloperoxidase activity or impaired motion in the kaolin-injected rat.. We show the first evidence that intra-articular injection of kaolin without CGN produced severe acute monoarthritis. This was highly dependent on substance P (released from C-fibres) and NK1 receptor activation, which stimulated local production of proinflammatory cytokines. This model may be of critical importance for mechanistic studies and screening new anti-inflammatory/analgesic drugs.

Topics: Animals; Animals, Newborn; Antidiarrheals; Arthritis; Capsaicin; Cytokines; Disease Models, Animal; Edema; Enzyme Inhibitors; Hyperalgesia; Indomethacin; Kaolin; Knee Joint; Male; Pain Measurement; Peroxidase; Piperidines; Quinuclidines; Rats; Rats, Wistar; Receptors, Neurokinin-1; Synovial Fluid

Affective disorders are common comorbidities of chronic inflammatory pain that are often overlooked in primary care. As the impact of inflammatory pain upon mood-like disorders in animal models is not well known, our objective was to assess whether prolonged experimental monoarthritis (ARTH) induced the development of anxiety and depressive-like behaviours in rodents and if amitriptyline, an antidepressant commonly used in the treatment of chronic pain, could reverse both nociceptive and mood-like impairments. Experimental ARTH was induced through an injection of kaolin/carrageenan into the right knee joint with control (SHAM) animals injected with saline. Four weeks after induction, ARTH animals displayed mechanical hyperalgesia and a depressive-like phenotype as they showed a significant increase in immobility and a decrease in the latency to immobility in the forced-swimming test at the expense of the time spent climbing/swimming. ARTH animals also displayed a decreased sucrose preference, an index of anhedonia and anxiety-like behaviour as time spent exploring the open arms of the elevated-plus-maze was decreased when compared to controls. The anxiety-like phenotype was also supported by an increase in the number of fecal boli left in the open field. In ARTH animals, the administration of amitriptyline decreased mechanical hyperalgesia and increased sucrose preference and the time spent climbing, although it had a deleterious effect in the performance of control animals. Our data show that this model of ARTH can be useful for the study of chronic pain-mood disorders comorbidities and that amitriptyline is able to partly reverse the associated nociceptive and emotional impairments.

Topics: Amitriptyline; Analgesics, Non-Narcotic; Animals; Arthritis; Carrageenan; Disease Models, Animal; Exploratory Behavior; Food Preferences; Hyperalgesia; Kaolin; Male; Maze Learning; Mood Disorders; Motor Activity; Pain Threshold; Physical Stimulation; Rats; Rats, Wistar; Swimming

Recently discovered neuropeptide S (NPS) has anxiolytic and pain-inhibiting effects in rodents. We showed previously that NPS increases synaptic inhibition of amygdala output to inhibit pain behaviors. The amygdala plays a key role in emotional-affective aspects of pain. Of clinical significance is that NPS can be applied nasally to exert anxiolytic effects in rodents. This study tested the novel hypothesis that nasal application of NPS can inhibit pain-related behaviors in an arthritis model through NPS receptors (NPSR) in the amygdala. Behaviors and electrophysiological activity of amygdala neurons were measured in adult male Sprague Dawley rats. Nasal application of NPS, but not saline, inhibited audible and ultrasonic vocalizations and had anxiolytic-like effects in the elevated plus-maze test in arthritic rats (kaolin/carrageenan knee joint arthritis model) but had no effect in normal rats. Stereotaxic application of a selective non-peptide NPSR antagonist (SHA68) into the amygdala by microdialysis reversed the inhibitory effects of NPS. NPS had no effect on hindlimb withdrawal thresholds. We showed previously that intra-amygdala application of an NPSR antagonist alone had no effect. Nasal application of NPS or stereotaxic application of NPS into the amygdala by microdialysis inhibited background and evoked activity of amygdala neurons in arthritic, but not normal, anesthetized rats. The inhibitory effect was blocked by a selective NPSR antagonist ([D-Cys(tBu)5]NPS). In conclusion, nasal application of NPS can inhibit emotional-affective, but not sensory, pain-related behaviors through an action in the amygdala. The beneficial effects of non-invasive NPS application may suggest translational potential.

Topics: Administration, Intranasal; Amygdala; Analgesics; Animals; Arthritis; Carrageenan; Disease Models, Animal; Hyperalgesia; Kaolin; Knee Joint; Male; Maze Learning; Neurons; Neuropeptides; Pain; Rats; Rats, Sprague-Dawley; Reflex; Spinal Cord; Vocalization, Animal

In chronic pain disorders, galanin (GAL) is able to either facilitate or inhibit nociception in the spinal cord but the contribution of supraspinal galanin to pain signalling is mostly unknown. The dorsomedial nucleus of the hypothalamus (DMH) is rich in galanin receptors (GALR) and is involved in behavioural hyperalgesia. In this study, we evaluated the contribution of supraspinal GAL to behavioural hyperalgesia in experimental monoarthritis.. In Wistar-Han males with a four week kaolin/carrageenan-induced monoarthritis (ARTH), paw-withdrawal latency (PWL) was assessed before and after DMH administration of exogenous GAL, a non-specific GALR antagonist (M40), a specific GALR1 agonist (M617) and a specific GALR2 antagonist (M871). Additionally, the analysis of c-Fos expression after GAL injection in the DMH was used to investigate the potential involvement of brainstem pain control centres. Finally, electrophysiological recordings were performed to evaluate whether pronociceptive On- or antinociceptive Off-like cells in the rostral ventromedial medulla (RVM) relay the effect of GAL.. Exogenous GAL in the DMH decreased PWL in ARTH and SHAM animals, an effect that was mimicked by a GALR1 agonist (M617). In SHAM animals, an unselective GALR antagonist (M40) increased PWL, while a GALR2 antagonist (M871) decreased PWL. M40 or M871 failed to influence PWL in ARTH animals. Exogenous GAL increased c-Fos expression in the RVM and dorsal raphe nucleus (DRN), with effects being more prominent in SHAM than ARTH animals. Exogenous GAL failed to influence activity of RVM On- or Off-like cells of SHAM and ARTH animals.. Overall, exogenous GAL in the DMH had a pronociceptive effect that is mediated by GALR1 in healthy and arthritic animals and is associated with alterations of c-Fos expression in RVM and DRN that are serotonergic brainstem nuclei known to be involved in the regulation of pain.

Topics: Analysis of Variance; Animals; Arthritis; Carrageenan; Evoked Potentials, Somatosensory; Galanin; Hyperalgesia; Hypothalamus; Kaolin; Male; Proto-Oncogene Proteins c-fos; Rats; Rats, Wistar; Reaction Time; Signal Transduction

Cannabinoids classically act via CB₁ and CB₂ receptors to modulate nociception; however, recent findings suggest that some cannabinoids bind to atypical receptors. One such receptor is GPR55 which is activated by the abnormal cannabidiol analogue O-1602. This study investigated whether the synthetic GPR55 agonist O-1602 can alter joint nociception in a rat model of acute joint inflammation. Acute (24 h) inflammatory joint pain was induced in male Wistar rats by intra-articular injection of 2% kaolin and 2% carrageenan. Single unit extracellular recordings were made from arthritic joint afferents in response to mechanical rotation of the knee. Peripheral administration of O-1602 significantly reduced movement-evoked firing of nociceptive C fibres and this effect was blocked by the GPR55 receptor antagonist O-1918. Co-administration of the CB₁ and CB₂ antagonists (AM281 and AM630 respectively) had no effect on O-1602 responses. This study clearly shows that atypical cannabinoid receptors are involved in joint nociception and these novel targets may be advantageous for the treatment of inflammatory pain.

Topics: Action Potentials; Acute Disease; Afferent Pathways; Animals; Arthritis; Cannabidiol; Carrageenan; Hindlimb; Joints; Kaolin; Male; Movement; Nerve Fibers, Unmyelinated; Nociception; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Receptors, G-Protein-Coupled

The amygdala plays an important role in the emotional-affective component of pain and in pain modulation. Group III metabotropic glutamate receptors (mGluRs) regulate pain-related activity in the amygdala, but the behavioral consequence and contribution of individual subtypes are not known yet. This study determined the effects of mGluR7 and mGluR8 activation in the central nucleus of the amygdala (CeA) on nocifensive and affective pain responses and on pain-related anxiety-like behavior of adult rats. The pain state was induced by intraarticular injections of kaolin/carrageenan into one knee joint to produce a localized monoarthritis. Subtype-selective agonists were administered into the CeA by microdialysis in normal rats and in rats with arthritis. An mGluR7-selective agonist (N,N'-dibenzyhydryl-ethane-1,2-diamine dihydrochloride, AMN082, 25microM) decreased spinal withdrawal reflex thresholds and increased audible and ultrasonic vocalizations evoked by brief (15s) compression of the knee. AMN082 also decreased the open-arm preference in the elevated plus maze (EPM) test, suggesting anxiety-like behavior. In arthritic animals, however, AMN082 failed to modulate the increased spinal reflexes and vocalizations and anxiety-like behavior. An mGluR8-selective agonist (S-3,4-dicarboxyphenylglycine, S-3,4-DCPG, 10microM) had no effect in normal animals but inhibited the increased spinal reflex responses and audible and ultrasonic vocalizations of arthritic rats. S-3,4-DCPG also increased the open-arm choices of arthritic rats, suggesting anxiolytic effects. The results suggest that under normal conditions mGluR7, but not mGluR8, facilitates pain responses and has anxiogenic properties whereas mGluR8, but not mGluR7, can inhibit nocifensive and affective behaviors and anxiety in a model of arthritic pain.

Topics: Amygdala; Animals; Arthritis; Behavior, Animal; Benzhydryl Compounds; Benzoates; Disease Models, Animal; Excitatory Amino Acid Agonists; Glycine; Kaolin; Male; Maze Learning; Microdialysis; Pain; Pain Measurement; Pain Threshold; Physical Stimulation; Rats; Rats, Sprague-Dawley; Receptors, Metabotropic Glutamate; Reflex

Hydrogen sulfide (H(2)S) is an endogenous gaseous mediator with the ability to modulate tissue inflammation and pain. The aim of this study was to determine the effect of an H(2)S donor (Na(2)S) on leukocyte-endothelium interactions, blood flow, and pain sensation in acutely inflamed knee joints. Acute arthritis was induced in urethane anesthetized C57bl/6 mice by intra-articular injection of kaolin/carrageenan (24-h recovery), and the effect of local administration of Na(2)S on leukocyte trafficking was measured by intravital microscopy. Synovial blood flow was measured in inflamed knees by laser Doppler perfusion imaging. Finally, the effect of an intra-articular injection of Na(2)S on joint pain in control and inflamed rats was determined by hindlimb incapacitance and von Frey hair algesiometry. Local administration of an H(2)S donor to inflamed knees caused a dose-dependent reduction in leukocyte adherence and an increase in leukocyte velocity. These effects could be inhibited by coadministration of the ATP-sensitive K(+) channel blocker glibenclamide. Local administration of Na(2)S to inflamed joints caused a pronounced vasoconstrictor response; however, there was no observable effect of Na(2)S on joint pain. These findings establish H(2)S as a novel signaling molecule in rodent knee joints. H(2)S exhibits potent anti-inflammatory properties, but with no detectable effect on joint pain.

Topics: Acute Disease; Animals; Arthritis; Behavior, Animal; Carrageenan; Cell Movement; Hydrogen Sulfide; Kaolin; Knee Joint; Leukocytes; Male; Mice; Mice, Inbred C57BL; Pain; Physical Stimulation; Proprioception; Signal Transduction; Sulfides

Joint mobilization is a common treatment used by healthcare professions for management of a variety of painful conditions, including inflammatory joint and muscle pain. We hypothesized that joint mobilization would reduce the bilateral hyperalgesia induced by muscle and joint inflammation. Mechanical hyperalgesia was measured by examining the mechanical withdrawal threshold of the rat's paw before and after induction of inflammation with 3% carrageenan (gastrocnemius muscle) or 3% kaolin/carrageenan (knee joint), and for 1 hour after knee joint mobilization. The mobilization consisted of rhythmically flexing and extending the knee joint to the end of range of extension while the tibia was simultaneously moved in an anterior to posterior direction. A bilateral decrease in mechanical withdrawal thresholds occurred 1, 2, and 4 weeks after inflammation of the knee joint or muscle. In animals with muscle inflammation, mobilization of the knee joint increased the mechanical withdrawal threshold bilaterally when given 1, 2, or 4 weeks after inflammation. However, in animals with knee joint inflammation, mobilization of the knee joint at 4 weeks increased the mechanical withdrawal threshold but had no effect when administered 1 or 2 weeks after inflammation. Therefore, joint mobilization reduces hyperalgesia induced by chronic inflammation of muscle and joint.. This article shows that unilateral joint mobilization reduces bilateral hyperalgesia induced by chronic muscle or joint inflammation. Understanding the pain conditions in which mobilization produces an analgesic effect should assist the clinician in selecting appropriate treatment techniques. The bilateral effect suggests that central mechanisms could mediate the analgesia.

Topics: Animals; Arthritis; Carrageenan; Chronic Disease; Hyperalgesia; Joints; Kaolin; Male; Myositis; Pain Measurement; Pain Threshold; Rats; Rats, Sprague-Dawley

The laterocapsular division of the central nucleus of the amygdala (CeA) is now defined as the "nociceptive amygdala" because of its high content of neurons that respond to painful stimuli. The majority of these neurons become sensitized in a model of arthritis pain. Here we address the role of G protein-coupled group I metabotropic glutamate receptor subtypes mGluR1 and mGluR5 in nociceptive processing under normal conditions and in pain-related sensitization. Extracellular single-unit recordings were made from 65 CeA neurons in anesthetized rats. Each neuron's responses to brief mechanical stimuli, background activity, receptive field size, and threshold were measured before and after induction of the kaolin/carrageenan mono-arthritis in one knee and before and during applications of agonists and antagonists into the CeA by microdialysis. All neurons received excitatory input from the knee(s) and responded most strongly to noxious stimuli. Before arthritis, a group I mGluR1 and mGluR5 agonist (DHPG, n = 10) potentiated the responses to innocuous and noxious stimuli. This effect was mimicked by an mGluR5 agonist (CHPG, n = 15). In the arthritis pain state (>6 h after induction), the facilitatory effects of DHPG (n = 9), but not CHPG (n = 7), increased. An mGluR1 antagonist (CPCCOEt) had no effect before arthritis (n = 12) but inhibited the responses of sensitized neurons in the arthritis pain state (n = 8). An mGluR5 antagonist (MPEP) inhibited brief nociceptive responses under normal conditions (n = 19) and prolonged nociception in arthritis (n = 8). These data suggest a change of mGluR1 function and activation in the amygdala in pain-related sensitization, whereas mGluR5 is involved in brief as well as prolonged nociception.

Topics: Action Potentials; Amygdala; Animals; Arthritis; Chromones; Dose-Response Relationship, Drug; Glycine; Kaolin; Male; Methoxyhydroxyphenylglycol; Neurons; Phenylacetates; Physical Stimulation; Pyridines; Rats; Rats, Sprague-Dawley; Receptor, Metabotropic Glutamate 5; Receptors, Metabotropic Glutamate

Response properties of nociceptors in the temporomandibular joint (TMJ) and surrounding area under experimental inflammation were investigated using an in vitro TMJ-nerve preparation in the rat. Nociceptive units (receptor and innervating nerve fiber) were classified into the following subtypes: Adelta-high-threshold mechanonociceptor (HTM), Adelta-polymodal nociceptor (POLY), C-HTM and C-POLY. In the inflamed joint, mechanical thresholds tended to be lower; however, the reaction to bradykinin was not identified as clearly as in control. Experimentally induced inflammation increased the proportion of heat-sensitive units and lowered heat threshold significantly. These results suggest that inflammation may sensitize nociceptors in the temporomandibular joint, and cause hyperalgesia and allodynia.

Topics: Action Potentials; Animals; Arthralgia; Arthritis; Bradykinin; Carrageenan; Disease Models, Animal; Hyperalgesia; Kaolin; Mechanoreceptors; Nerve Fibers, Myelinated; Nerve Fibers, Unmyelinated; Nociceptors; Pain Threshold; Physical Stimulation; Rats; Rats, Wistar; Sensory Receptor Cells; Temporomandibular Joint; Temporomandibular Joint Disorders

Inflammatory pain is caused by sensitization of peripheral and central nociceptive neurons. Prostaglandins substantially contribute to neuronal sensitization at both sites. Prostaglandin E2 (PGE2) applied to the spinal cord causes neuronal hyperexcitability similar to peripheral inflammation. Because PGE2 can act through EP1-EP4 receptors, we addressed the role of these receptors in the spinal cord on the development of spinal hyperexcitability. Recordings were made from nociceptive dorsal horn neurons with main input from the knee joint, and responses of the neurons to noxious and innocuous stimulation of the knee, ankle, and paw were studied after spinal application of recently developed specific EP1-EP4 receptor agonists. Under normal conditions, spinal application of agonists at EP1, EP2, and EP4 receptors induced spinal hyperexcitability similar to PGE2. Interestingly, the effect of spinal EP receptor activation changed during joint inflammation. When the knee joint had been inflamed 7-11 hr before the recordings, only activation of the EP1 receptor caused additional facilitation, whereas spinal application of EP2 and EP4 receptor agonists had no effect. Additionally, an EP3alpha receptor agonist reduced responses to mechanical stimulation. The latter also attenuated spinal hyperexcitability induced by spinal PGE2. In isolated DRG neurons, the EP3alpha agonist reduced the facilitatory effect of PGE2 on TTX-resistant sodium currents. Thus pronociceptive effects of spinal PGE2 can be limited, particularly under inflammatory conditions, through activation of an inhibitory splice variant of the EP3 receptor. The latter might be an interesting target for controlling spinal hyperexcitability in inflammatory pain states.

Topics: Animals; Arthritis; Carrageenan; Cell Separation; Dinoprostone; Disease Models, Animal; Ganglia, Spinal; Kaolin; Knee Joint; Male; Neurons; Pain; Patch-Clamp Techniques; Physical Stimulation; Protein Isoforms; Rats; Rats, Wistar; Receptors, Prostaglandin E; Receptors, Prostaglandin E, EP3 Subtype; Spinal Cord

The latero-capsular division of the central nucleus of the amygdala (CeA) is now defined as the 'nociceptive amygdala' because of its high content of neurons activated exclusively or preferentially by noxious stimuli. Multireceptive (MR) neurons that respond to innocuous and, more strongly, to noxious stimuli become sensitized in arthritis pain. This form of nociceptive plasticity involves presynaptic group I metabotropic glutamate receptors, which increase glutamate release. Here we address the role of N-methyl-D-aspartate (NMDA) and non-NMDA receptors. Extracellular single-unit recordings were made from 25 CeA neurons in anesthetized rats. The neurons' responses to graded brief (15 s) mechanical stimuli, background activity, receptive field size and threshold were measured before and after the induction of kaolin/carrageenan arthritis in one knee and before and during drug applications into the CeA by microdialysis. All neurons examined received excitatory input from the knee(s) and were MR neurons. A selective NMDA receptor antagonist (AP5) inhibited responses to noxious stimuli more potently in the arthritic pain state (n = 6) than under control conditions before arthritis (n = 8) AP5 also inhibited the enhanced background activity and increased responses to normally innocuous stimuli in arthritis, but had no significant effects on these parameters under control conditions. A selective non-NMDA receptor antagonist (NBQX) inhibited background activity and evoked responses under normal control conditions (n = 6) and in arthritis (n = 8) These data suggest that activation of both NMDA and non-NMDA receptors contributes to pain-related sensitization of amygdala neurons.

Topics: 2-Amino-5-phosphonovalerate; Action Potentials; Amygdala; Analysis of Variance; Animals; Arthritis; Disease Models, Animal; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists; Kaolin; Male; Neural Inhibition; Neurons; Nociceptors; Pain; Pain Measurement; Physical Stimulation; Quinoxalines; Rats; Rats, Sprague-Dawley; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate

Since pain is an important symptom in arthritis, useful behavioral indices for pain in experimental arthritis animal models are important tools for investigative work on arthritis. The purpose of this study was to develop simple and quantifiable behavioral tests, which would represent the level of arthritic pain that develops after induction of inflammation in the knee. Two models of knee joint arthritis were produced: (1) KC model-injection of kaolin and carrageenan into the synovial cavity of the knee, and (2) CFA model-injection of complete Freund's adjuvant into the synovial cavity of the knee. The following three variables were measured before and at various times after the induction of arthritis. As an estimate of the degree of edema, the circumference of the knee was measured. As pain indices, (1) the vocalization threshold of compression force applied to the knee joint was measured to represent tenderness of the joint, and (2) the struggle threshold of the knee extension angle was measured to represent a reduction in range of motion in the arthritic joint. A time course study showed that behavioral changes last for at least 1 week for the KC model and at least 2 weeks for the CFA model. Correlation studies showed that all three variables significantly correlated with each other in both the KC and CFA arthritic models. Systemically injected morphine produced a partial reversal of these indices with the expected time course and dose response of a morphine-induced analgesic. It is concluded that two variables, the struggle threshold for knee extension and the vocalization threshold for knee compression, could be used as simple and useful pain indices in experimental models of arthritis.

Topics: Analgesics, Opioid; Animals; Arthritis; Biomechanical Phenomena; Carrageenan; Disease Models, Animal; Edema; Freund's Adjuvant; Kaolin; Knee Joint; Male; Morphine; Motor Activity; Pain; Pain Measurement; Pain Threshold; Range of Motion, Articular; Rats; Rats, Sprague-Dawley; Stress, Psychological; Vocalization, Animal

This study examined the release of several amino acids after induction of knee joint inflammation in rats using kaolin and carrageenan. During the initial 10-min collection after knee joint injection with the irritants, the concentration of glutamate and the nitric oxide metabolites, arginine and citrulline, doubled. This increase persisted for at least two hours. During the same time period aspartate concentrations remained unchanged. Direct knee joint administration of lidocaine prevented the increases in amino acid concentration measurable by microdialysis probe inserted into the joint. These data suggest the possibility that glutamate may be released by neuronal endings in the joint.

Topics: Amino Acids; Anesthetics, Local; Animals; Arginine; Arthritis; Carrageenan; Chromatography, High Pressure Liquid; Citrulline; Glutamic Acid; Hindlimb; Injections, Intra-Articular; Joints; Kaolin; Lidocaine; Male; Pain; Rats; Rats, Sprague-Dawley; Synovial Fluid

Transcutaneous electrical nerve stimulation (TENS) is commonly used for relief of pain. The literature on the clinical application of TENS is extensive. However, surprisingly few reports have addressed the neurophysiological basis for the actions of TENS. The gate control theory of pain is typically used to explain the actions of high-frequency TENS, whereas, low-frequency TENS is typically explained by release of endogenous opioids. The current study investigated the role of mu, delta, and kappa opioid receptors in antihyperalgesia produced by low- and high-frequency TENS by using an animal model of inflammation. Antagonists to mu (naloxone), delta (naltrinodole), or kappa (nor-binaltorphimine) opioid receptors were delivered to the spinal cord by microdialysis. Joint inflammation was induced by injection of kaolin and carrageenan into the knee-joint cavity. Withdrawal latency to heat was assessed before inflammation, during inflammation, after drug (or artificial cerebral spinal fluid as a control) administration, and after drug (or artificial cerebral spinal fluid) administration + TENS. Either high- (100 Hz) or low- frequency (4 Hz) TENS produced approximately 100% inhibition of hyperalgesia. Low doses of naloxone, selective for mu opioid receptors, blocked the antihyperalgesia produced by low-frequency TENS. High doses of naloxone, which also block delta and kappa opioid receptors, prevented the antihyperalgesia produced by high-frequency TENS. Spinal blockade of delta opioid receptors dose-dependently prevented the antihyperalgesia produced by high-frequency TENS. In contrast, blockade of kappa opioid receptors had no effect on the antihyperalgesia produced by either low- or high-frequency TENS. Thus, low-frequency TENS produces antihyperalgesia through mu opioid receptors and high-frequency TENS produces antihyperalgesia through delta opioid receptors in the spinal cord.

Topics: Animals; Arthritis; Behavior, Animal; Carrageenan; Injections, Intra-Articular; Kaolin; Male; Microdialysis; Naloxone; Naltrexone; Narcotic Antagonists; Rats; Rats, Sprague-Dawley; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu; Spinal Cord; Transcutaneous Electric Nerve Stimulation

Intrathecal (i.t.) administration of the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline enhances pain behaviors in the formalin test. This study examined whether bicuculline also increases the peripheral inflammation induced by formalin. Subcutaneous injection of 0.25 to 5.0% formalin in the plantar surface of one hindpaw of the rat produced a concentration-dependent increase in plasma extravasation as measured by the Evans Blue method. Pretreatment with 0.3 microg i.t. bicuculline neither enhanced nor suppressed formalin-induced plasma extravasation. This dose of bicuculline also did not affect plasma extravasation induced by injection of 3% kaolin/3% carrageenan in the knee of the rat. These data indicate that the enhancement of formalin-induced pain behaviors by i.t. bicuculline is not secondary to enhanced peripheral inflammation, but more likely reflects enhancement of nociceptive transmission in the spinal cord.

Topics: Animals; Arthritis; Bicuculline; Carrageenan; Coloring Agents; Evans Blue; Extravasation of Diagnostic and Therapeutic Materials; GABA Antagonists; Hindlimb; Inflammation; Injections, Spinal; Kaolin; Knee Joint; Male; Pain Measurement; Rats; Rats, Sprague-Dawley

In spinal cord neurons in anesthetized rats, the role on neurokinin A and neurokinin-2 receptors in the processing of nociceptive information from the knee joint was studied. The specific non-peptide antagonist at the neurokinin-2 receptor, SR48968, its inactive R-enantiomer, SR48965, neurokinin A, substance P and (RS)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), were administered ionophoretically close to neurons with input from the knee joint. SR48968 reduced the effects of exogenous neurokinin A, but not those of exogenous substance P and AMPA, indicating selective blockade of neurokinin-2 receptors. In most neurons with input from the normal knee joint, SR48968 reduced dose-dependently the responses to noxious pressure with applied to the knee, and in approximately 50% of the neurons the responses to innocuous pressure. The administration of SR48968 during the induction of an experimental joint inflammation markedly attenuated the development of inflammation-evoked hyperexcitability. In hyperexcitable neurons with input from the inflamed joint, SR48968 reduced the responses to noxious and innocuous pressure. The relative reduction of the responses was more pronounced than in neurons with input from the normal joint. None of the effects of SR48968 was mimicked by SR48965. These data show that neurokinin-2 receptors are involved in the spinal processing of nociceptive information from the normal joint. Furthermore, neurokinin-2 receptors must be coactivated at an early stage of inflammation, to allow the generation of hyperexcitability. Finally, neurokinin-2 receptors are involved in maintenance of hyperexcitability during inflammation. In summary, spinal neurokinin-2 receptors are important in the generation of pain in the normal and inflamed joint.

Topics: alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Animals; Arthritis; Benzamides; Carrageenan; Hyperalgesia; Iontophoresis; Kaolin; Knee Joint; Male; Neurokinin A; Nociceptors; Pain; Piperidines; Pressure; Rats; Rats, Wistar; Receptors, Neurokinin-2; Spinal Cord; Substance P

Pharmacological studies have implicated the spinal activation of excitatory amino acids, nitric oxide, and prostaglandins systems in the development of tactile and thermal hypersensitivity and central sensitization after peripheral inflammation. In the present study, using a chronically placed loop dialysis catheter, we examined in the unanesthetized rat the effect of carrageenan/kaolin (C/K)-induced knee joint inflammation on the time course of spinal release of several active factors including excitatory amino acids (glutamate, aspartate), citrulline (a marker of nitric oxide formation), and prostaglandin E2 (PGE2) as well as the concomitant development of tactile and thermal hypersensitivity. Infection of C/K in the knee evoked a significant release of glutamate, with an initial peak seen immediately after knee C/K injection (179 +/- 22%) and with a progressive and consistent increase over a period of 24 h (153-186%). Comparable changes in the concentration of aspartate (123-179%) were observed. Citrulline was constantly above baseline for the 24-h period (121-158%). PGE2 was significantly increased at 10 min (146 +/- 11%) with no change observed between 3-5 h. At 24 h, PGE2 was again significantly (143 +/- 18%) increased. Behaviorally, a prominent thermal and tactile allodynia developed after injection with the peak seen by 1-3 h after induction of the inflammation. This hypersensitivity state, while diminished in its intensity, persisted for the entire observation period. These data suggest that increased spinal release of excitatory amino acids (EAA), nitric oxide and/or PGE2 is involved in the maintenance of the pain state initiated by acute peripheral inflammation.

Topics: Amino Acids; Animals; Arthritis; Carrageenan; Citrulline; Dinoprostone; Drug Combinations; Hot Temperature; Injections, Intra-Articular; Kaolin; Male; Microdialysis; Physical Stimulation; Rats; Rats, Sprague-Dawley; Sodium Chloride; Spinal Cord; Time Factors; Touch

1. Injection of kaolin and carrageenan into the knee joint of cats or monkeys resulted in an acute inflammation. Four hours after injection of the knee joint, efferent activity could be evoked in articular afferent fibers and in dorsal root filaments. We interpret this efferent activity to be dorsal root reflexes (DRRs). Under our experimental conditions, the DRRs were generally synchronized compound action potentials, although in some cases single-unit activity was also observed. 2. DRRs were not produced in animals with uninflamed knee joints and normal body temperatures. 3. Recordings from two different sites on cut dorsal root filaments ipsilateral to the inflamed knee joint allowed the determination of the conduction velocities of groups of afferent fibers carrying DRRs. The DRRs occurred in A beta-, A delta-, and C fibers. However, in these experiments the peripheral destination of the afferent fibers was unknown. 4. To prove that DRRs occurred in joint afferents, recordings were made from two different sites on the proximal stump of the medial articular nerve that innervated the inflamed knee. The DRRs were again found in all fiber types, i.e., group II, III, and IV (A beta, A delta, and C) articular afferent fibers. 5. Compound DRRs were recorded from the central end of a cut dorsal root filament after electrical stimulation at C fiber intensity of a dorsal root adjacent to the filament. This DRR activity was eliminated by extensive dorsal rhizotomies of the L2-S1 roots.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Action Potentials; Afferent Pathways; Animals; Arthritis; Cats; Disease Models, Animal; Efferent Pathways; Ganglia, Spinal; Inflammation; Joints; Kaolin; Macaca mulatta; Nerve Fibers; Reflex

This study addressed the intraspinal release of immunoreactive calcitonin gene-related peptide in vivo during mechanical stimulation of the normal joint and during the development of an acute experimental inflammation in the knee joint in the anaesthetized cat (spinalized) and rat (not spinalized). Release was assessed using microprobes coated with antibody to calcitonin gene-related peptide; inhibition of binding of [125I]calcitonin gene-related peptide to these probes following insertion into the spinal cord is equated with intraspinal release of the endogenous (unlabelled) peptide. Probes inserted prior to inflammation showed marked basal release of immunoreactive calcitonin gene-related peptide in the dorsal horn with a maximum in the superficial dorsal horn in the absence of intentional stimulation. The pattern of binding of [125I]calcitonin gene-related peptide was not or only minimally changed by innocuous mechanical stimuli (flexion of and innocuous pressure to the knee in the cat and innocuous pressure to the knee of the rat) but was significantly altered by electrical stimulation of the tibial nerve in the cat (sufficient to excite unmyelinated afferent fibres), indicating release of the peptide by the latter stimulus. During the first hours of the development of an experimental inflammation in the knee joint induced by intra-articular injections of kaolin and carrageenan, the pattern of binding of [125I]calcitonin gene-related peptide changed. In the cat, the level of immunoreactive calcitonin gene-related peptide showed a persistent increase in the gray matter and up to the surface of the cord and release was slightly increased by innocuous stimuli. In the rat, increased levels of immunoreactive calcitonin gene-related peptide were mainly seen in the superficial and deep dorsal horn during innocuous pressure (this stimulus did not evoke release of the peptide prior to inflammation) and noxious pressure applied to the injected knee, whereas increased basal levels were only observed at later stages. These data show that the development of an acute experimental inflammation in the joint is associated with an enhancement of the intraspinal release of immunoreactive calcitonin gene-related peptide. Since the changes in the release were noted at an early stage, within the first hours, they could contribute to the generation of inflammation-evoked changes of the responsiveness of spinal cord neurons and hence to the mechanisms inducing inflammatory p

Topics: Animals; Antibodies; Arthritis; Calcitonin Gene-Related Peptide; Carrageenan; Cats; Electric Stimulation; Kaolin; Knee Joint; Male; Physical Stimulation; Rats; Rats, Wistar; Reference Values; Spinal Cord; Tibial Nerve

To investigate the role of primary afferents, sympathetic postganglionic efferents and descending systems on the central control of peripheral inflammation.. Acute inflammation was induced by intra-articular injection of kaolin and carrageenan into the knee joint cavity of the rat. Before the induction of the arthritis, a unilateral dorsal rhizotomy, a chemical (phentolamine) and/or surgical sympathectomy, or a spinal transection was performed. Joint inflammation (joint circumference and thermographic readings) and behavioural signs were assessed.. Only arthritic animals with a dorsal rhizotomy showed a significant reduction of the inflammatory response compared with control arthritic animals. No significant differences in the inflammatory response occurred following sympathectomy or spinal transection. The animals who received sympathectomy showed similar behavioural manifestations to the arthritic animals.. The central terminals of primary afferents are important in the development of acute joint inflammation since dorsal rhizotomy attenuated the inflammatory response in the knee joint. The sympathetic nervous system is not involved in the acute inflammatory phase of this arthritis model. The central processes controlling acute inflammation involve a local spinal circuit since spinal cord transection at T9 has no effect on the inflammation.

Topics: Acute Disease; Animals; Arthritis; Behavior, Animal; Carrageenan; Kaolin; Male; Neurons, Afferent; Neurons, Efferent; Pain; Rats; Rats, Sprague-Dawley; Spinal Cord; Thermography

Efferent activity was recorded in knee joint afferents in response to mechanical stimulation of the hindlimb following induction of acute arthritis. The activity was abolished by application of lidocaine or crushing the nerve proximally and by dorsal rhizotomy but not by sympathectomy. It was concluded that this activity represents dorsal root reflexes in response to natural stimulation of the hindlimb. We propose that increased activity of articular afferents and of dorsal horn neurons during arthritis results in the pathological activation of the central terminals of primary afferents by enhancing primary afferent depolarization. Dorsal root reflexes could then release substances in the knee joint and thus contribute to the acute inflammatory response.

Topics: Action Potentials; Animals; Arthritis; Carrageenan; Denervation; Foot; Ganglia, Spinal; Kaolin; Knee Joint; Lidocaine; Male; Nerve Crush; Pressure; Rats; Rats, Sprague-Dawley; Reflex; Tarsus, Animal

Release of excitatory amino acids (EAA's) in the dorsal horn of awake rats was monitored by microdialysis during the development of arthritis induced by injection of 3% kaolin and 3% carrageenan into the knee joint. Concentrations of EAA's in the dialysate samples were measured by high performance liquid chromatography at baseline, during delivery of EAA antagonists, and for the first 8 h of arthritis. An initial increase in aspartate (ASP) and glutamate (GLU) was observed on injection of the knee joint in rats made arthritic. Subsequently, there was a prolonged release phase after 3 h which persisted at least 8 h. Specific EAA antagonists to non-N-methyl-D-aspartate (non-NMDA; CNQX) and to NMDA (AP7) receptors were used to block the effects seen in the untreated arthritic animals. The increase in ASP and GLU release seen at the time of injection in untreated arthritic animals did not occur in arthritic animals treated with EAA receptor antagonists (CNQX or AP7). In arthritic animals treated with CNQX, the prolonged release phase was delayed and attenuated for GLU and decreased below baseline for ASP. In the AP7-treated arthritic animals, no change from baseline concentration was observed for ASP until 7 h, and GLU decreased minimally. The data indicate that this arthritis model is accompanied by an initial increased release of EAA's at the time of injection which is dependent on the activation of both non-NMDA and NMDA receptors. Subsequent development of arthritis, manifested as an inflamed joint and a delayed and prolonged release of ASP and GLU, is dependent on the initial activation of these EAA receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 2-Amino-5-phosphonovalerate; 6-Cyano-7-nitroquinoxaline-2,3-dione; Amino Acids; Animals; Arthritis; Aspartic Acid; Carrageenan; Glutamates; Glutamic Acid; Injections, Intra-Articular; Kaolin; Knee Joint; Male; N-Methylaspartate; Quinoxalines; Rats; Rats, Sprague-Dawley; Spinal Cord

Knee joint injection of kaolin and carrageenan produces acute inflammation with localized joint swelling and increased temperature. This inflammation results in behavioral changes, including limping and guarding of the limb, and heat hyperalgesia. Prior spinal cord infusion of bicuculline, a gamma amino butyric acidA (GABAA) receptor antagonist, significantly reduces the severity of joint inflammation and prevents the development of heat hyperalgesia. In contrast, infusion of a GABAB receptor antagonist does not alter the arthritis. Therefore, these data support the existence of a central pathway involving GABAA receptors in the spinal cord that influences the development of peripheral inflammation. We suggest that primary afferent depolarization and accompanying dorsal root reflexes play a significant role in the development of peripheral inflammation.

Topics: Animals; Arthritis; Behavior, Animal; Bicuculline; Carrageenan; GABA Antagonists; Hot Temperature; Hyperalgesia; Injections; Kaolin; Microdialysis; Organophosphorus Compounds; Rats; Receptors, GABA; Spinal Cord

The antireactive activity of glucosamine sulfate (GS) (CAS 29031-19-4) was tested in the rat in experimental models of subacute inflammation (sponge granuloma and croton oil granuloma), on subacute mechanical arthritis (kaolin arthritis) and in immunological-reactive arthritis and generalized inflammation (adjuvant arthritis). On these models GS was found effective in oral daily doses of 50-800 mg/kg. Tne potency of GS in comparison of that of indometacin used in the same tests as reference substance was found 50-300 times lower. Since, however, the toxicity of indometacin in chronic toxicity experiments is 1000-4000 times larger, the therapeutic margin with regard to prolonged treatments of inflammatory disorders results 10-30 times more favourable for GS than for indometacin. GS can therefore be considered as a drug of choice for prolonged oral treatment of rheumatic disorders.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Arthritis, Experimental; Croton Oil; Glucosamine; Granuloma; Indomethacin; Joints; Kaolin; Male; Rats; Rats, Inbred Strains

Antibody microprobes were used to study the release of immunoreactive neurokinin A into the spinal cord of anaesthetised cats during and following injection of a knee joint with kaolin and carrageenan. A basal level of immunoreactive neurokinin A was detected prior to any noxious stimuli. Innocuous mechanical joint stimuli (flexion or pressure) did not alter this basal level of release. However, on injection of kaolin and carrageenan into a knee joint, evidence of release into the ipsilateral spinal cord was immediately observed. Initially, immunoreactive neurokinin A was detected in 2 regions: one at the dorsal surface of the spinal cord and the other centred on the superficial dorsal horn. Within 1 h of joint injection, however, immunoreactive neurokinin A was detected throughout the dorsal horn and the adjacent white matter. The extensive spread and persistence of immunoreactive neurokinin A in the spinal cord may underlie some of the prolonged excitability changes evoked by brief noxious stimuli and peripheral inflammation reported by other laboratories.

Topics: Acute Disease; Animals; Arthritis; Autoradiography; Carrageenan; Cats; Disease Models, Animal; Kaolin; Molecular Probes; Neurokinin A; Spinal Cord; Stress, Mechanical

Plasma levels of some arachidonic acid metabolites were investigated in acute and chronic models of inflammation in rats. As a model of chronic inflammation, adjuvant arthritis in rats induced by the injection of Freund's complete adjuvant, and as an acute model for inflammation, kaolin-induced paw oedama were used. Plasma leukotriene(LT) C4-like and prostaglandin(PG) E2-like activities were quantitated by bioassay in guinea-pig ileum and rat stomach fundus respectively. In the course of adjuvant arthritis, plasma levels of LTC4- and PGEi2-like activities were increased. Plasma LTC4-like activity reached a maximum within 3 weeks, while PGE2-like activity reached a maximum 10 days after adjuvant injection. In the early phase of adjuvant arthritis, levels of both LTC4- and PGE2-like activities were found to be low but both activities were increased in the late phase of inflammation.

Topics: Animals; Arthritis; Arthritis, Experimental; Biological Assay; Dinoprostone; Edema; Gastric Fundus; Guinea Pigs; Ileum; Kaolin; Rats; SRS-A

In cats the injections of kaolin and carrageenan into the knee joint lead to an acute arthritis which develops within 1-3 hours. In parallel articular afferents (low, high threshold and unresponsive ones) are becoming (more) sensitive to movements in the working range of the joint and many show (enhanced) ongoing discharges. Consequently spinal nociceptive-specific and wide dynamic range neurons with afferent input from the inflamed knee develop (increased) responsiveness to gentle stimulation of the joint. But in addition most of these neurons display enhanced reactions to non-inflamed parts of their receptive fields, too, and some neurons show enlargement of their total receptive fields. These latter findings indicate that the sensitization of spinal neurons is not simply reflecting the increased afferent input from the inflamed knee but that intrinsic spinal mechanisms may participate in the sensitization process.

Topics: Animals; Arthritis; Carrageenan; Cats; Hindlimb; Joints; Kaolin; Neurons, Afferent; Nociceptors; Spinal Cord

Recordings were made from 16 ascending tract cells in the spinal cords of anaesthetized, spinalized cats before and after an acute arthritis was produced by injection of kaolin and carrageenan into the knee joint. The responses tested routinely were to passive flexion of the knee, an innocuous movement. In some cases, responses to other movements were also tested, and changes in background discharge rates were monitored. Control recordings for a period of 1 h or in 3 cases of 3 h indicated that the responses to flexion were reasonably stationary. Four tract cells that initially showed little or no response to flexion of the knee joint developed large responses within 1 to 2 h after inflammation of the joint. Another 9 cells were tested that had responses to flexion of the knee joint prior to inflammation. In 6 cases, inflammation produced enhanced static or transient responses. In 2 cases, the effect of flexion was initially inhibitory or variable, but after inflammation these cells showed large excitatory responses. In the other case, inflammation had no effect. Background discharges were increased by inflammation in 6 of these 9 cells. The effect of inflammation of the knee joint was tested on 3 tract cells that had no clearly defined receptive field in the knee. In 1 case, a response developed to knee flexion after acute inflammation was produced. In the other 2 cases, there were initially responses to knee flexion, but these were unchanged by inflammation. Two of the cells tested had bilateral receptive fields in or around the knee joints. Inflammation of one knee joint enhanced the responses to flexion of the same but not of the contralateral knee in one case but greatly increased the responses to flexion of both knees in the other case. Injections of prostaglandin (PGE2) caused an enhancement of the responses to knee flexion beyond that caused by inflammation in 5 of 7 cases. One cell whose responses to flexion of the knee were unaffected by inflammation showed inhibitory responses to prostaglandin injections into the inflamed knee joint. The effects of inflammation on the responses of ascending tract cells of the spinal cord appear to serve as a useful neural model of the events responsible for the development of arthritic pain.

Topics: Acute Disease; Afferent Pathways; Animals; Arthritis; Carrageenan; Cats; Dinoprostone; Kaolin; Knee Joint; Nociceptors; Pain; Prostaglandins E; Spinal Cord

Topics: Animals; Arthritis; Arthritis, Experimental; Edema; Gold; Kaolin; Male; Rats

Geophagia, the consumption of nonnutritive dirt, has previously been shown to be increased when rats have been made acutely ill. The present paper reports two experiments in which geophagia in response to stress and arthritis was measured. In the first experiment, experimental rats were injected with Freund's Complete Adjuvant (FCA), a mineral oil suspension of killed Mycobacterium butyricum. They ate significantly more kaolin (a nonnutritive substance) than controls, suggesting that geophagia is a behavioral measure of illness. In a second study, kaolin consumption was similarly elevated in stressed and/or arthritic animals as well as in control rats living in the same room. Nonstressed controls housed in a remote room ate significantly less kaolin than rats in all other groups. It was concluded that geophagia may occur in response to any homeostatic alteration (stress state). Furthermore, this state can presumably be communicated to naive rats from adjacently-housed stressed animals. Geophagia was postulated to occur in animals who experience a generalized stress reponse since this state may involve gastro-intestinal malaise.

Topics: Acacia; Animals; Arthritis; Arthritis, Experimental; Cold Temperature; Humans; Kaolin; Male; Pica; Rats; Stress, Physiological

The mild analgesic activities of aspirin, phenacetin and acetaminophen have been compared in the trypsin, kaolin and carrageenan hyperalgesic assays as well as in the acetic acid writhing test. The trypsin and kaolin hyperalgesic assays were designed to be unaffected by drugs with anti-inflammatory activity. Aspirin and acetaminophen were inactive in these two tests at dose levels devoid of side effects. Phenacetin was active in the trypsin and kaolin assays with oral ED50's of 114 +/- 36.2 and 107 +/- 11.5 mg/kg, respectively. Non-steroidal anti-inflammatory drugs as well as phenacetin and acetaminophen were active in the acetic acid writhing and carrageenan hyperalgesic assays. This led to evaluation of phenacetin and acetaminophen as anti-inflammatory agents. Both of these latter drugs were active in the carrageenan pleurisy and adjuvant arthritis models of inflammation. In all studies phenacetin was equipotent to or more potent than acetaminophen. The data suggest that the analgesia produced by aspirin and acetaminophen results from their anti-inflammatory activity whereas the analgesia produced by phenacetin has two components, one dependent on and one independent of anti-inflammatory activity.

Topics: Acetaminophen; Acetates; Analgesics; Animals; Anti-Inflammatory Agents; Arthritis; Aspirin; Carrageenan; Kaolin; Male; Models, Biological; Pain; Phenacetin; Pleurisy; Rats; Trypsin

Topics: Animals; Anthelmintics; Anti-Inflammatory Agents; Arthritis; Disease Models, Animal; Dracunculiasis; Edema; Imidazoles; Kaolin; Niridazole; Pleurisy; Rats; Thiazoles; Turpentine

Topics: Animals; Anti-Inflammatory Agents; Arthritis; Edema; Hindlimb; Hyaluronoglucosaminidase; Kaolin; Male; Plethysmography; Polysaccharides; Rats; Time Factors

Topics: Acetates; Animals; Anti-Inflammatory Agents; Antifungal Agents; Arthritis; Carrageenan; Chymotrypsin; Dextrans; Edema; Fatty Acids; Formaldehyde; Hindlimb; Irritants; Kaolin; Lactones; Male; Mustard Plant; Plants, Medicinal; Rats; Yeasts

Topics: Animals; Anthracenes; Arthritis; Carrageenan; Chlorpromazine; Diazepam; Edema; Foot; Hindlimb; Inflammation; Kaolin; Male; Pleurisy; Rats; Rats, Inbred Strains; Tranquilizing Agents; Turpentine

Topics: Acetylcholine; Administration, Topical; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antifungal Agents; Arthritis; Arthrodermataceae; Bacteria; Blood Pressure; Burns; Candida; Candidiasis; Carrageenan; Depression, Chemical; Dextrans; Gastrointestinal Motility; Guinea Pigs; Hindlimb; Kaolin; Mice; Rabbits; Rats; Staphylococcal Infections; Thiourea

Topics: Animals; Arthritis; Arthus Reaction; Bradykinin; Capillary Permeability; Carrageenan; Depression, Chemical; Dextrans; Disease Models, Animal; Dogs; Edema; Exudates and Transudates; Female; Formaldehyde; Granuloma; Guinea Pigs; Histamine; Hyaluronoglucosaminidase; Kaolin; Lymph; Male; Mice; Mycobacterium Infections; Ovalbumin; p-Methoxy-N-methylphenethylamine; Phytotherapy; Plants, Medicinal; Rabbits; Rats; Serotonin; Species Specificity; Swine

Topics: Allopurinol; Animals; Anti-Inflammatory Agents; Arthritis; Edema; Kaolin; Male; Models, Biological; Pleurisy; Rats; Turpentine; Xanthine Oxidase

Topics: Animals; Anti-Inflammatory Agents; Arthritis; Arthritis, Experimental; Binding Sites; Carrageenan; Foot Diseases; Formaldehyde; Freund's Adjuvant; Kaolin; Leukocyte Count; Pharmacology; Phenylbutazone; Rats; Research; Thiazoles; Toxicology; Tuberculin Test

Topics: Arthritis; Arthritis, Rheumatoid; Collagen Diseases; Diagnosis; gamma-Globulins; Hemagglutination; Hemagglutination Tests; Humans; Immune Sera; Kaolin; Rheumatoid Factor; Serology