Disease diagnosis in horses involves the identification and characterization of illnesses through various diagnostic methods and tools. This process is essential for effective veterinary care and management of equine health. Techniques used in diagnosing diseases in horses include clinical examinations, laboratory tests, imaging modalities such as ultrasonography and radiography, and molecular diagnostics. Blood tests are frequently utilized to assess parameters such as complete blood count and biochemical profiles, which can indicate underlying health issues. Additionally, advancements in genetic testing and biomarker identification have enhanced the ability to detect specific diseases early. This page aggregates peer-reviewed research studies and scholarly articles that explore diagnostic methodologies, their applications, and their impact on equine health management.
Durham AE, Smitht KC, Newton JR, Hillyer MH, Hillyer LL, Smith MR, Marr CM.The study was designed to investigate the prognostic value of liver biopsy during investigation of cases of suspected liver disease in mature horses. Objective: That liver biopsy is the most prognostically useful technique in common usage in the investigation of suspected liver disease. Methods: This study examined the prognostic value of liver biopsy during the investigation of suspected liver disease in 73 mature horses. Histopathological variables comprising fibrosis, irreversible cytopathology, inflammatory infiltration, haemosiderin accumulation and biliary hyperplasia were found to be si...
Chandler KJ, Billson FM, Mellor DJ.Ophthalmic lesions were detected in 67 of 83 horses and ponies aged 15 years or more. Degeneration of the vitreous, followed by senile retinopathy, were the most common lesions and both of them became more common with advancing age, although few of the owners reported disturbances of vision in their animals.
Stanley SD, McKemie D, Skinner W.A rapid, sensitive, and rugged method for detecting drugs and drug metabolites in extracts of horse urine is described. The use of large-volume injection (LVI) gas chromatography-mass spectrometry (GC-MS) for analysis of horse urine extracts allowed automation of the derivatization procedure and reduction of the sample volume from 5 mL to 1 mL of urine. An autosampler and temperature-programmable inlet were used to automatically dissolve the sample extract and form trimethylsilyl derivatives of over 200 analytes. The suitability of this procedure for routine GC-MS detection of approximately 80...
Durham AE, Smith KC, Newton JR.The diagnostic value of several investigative procedures commonly used during the evaluation of suspected equine hepatopathy cases has not been specifically quantified in previous studies. Objective: No noninvasive procedures would clearly discriminate between horses with and without significant liver disease. Methods: Histopathology of biopsy samples was used as the 'gold standard' technique for definitive diagnosis of the presence or absence of significant liver disease. Clinical, ultrasonographic and clinicopathological data obtained during the investigation of 82 suspected cases of hepatop...
Durham AE, Newton JR, Smith KC, Hillyer MH, Hillyer LL, Smith MR, Marr CM.Results of noninvasive tests of liver disease do not always correlate with the degree of hepatic disease nor outcome of the case. Objective: To investigate the prognostic value of data collected using noninvasive tests during the investigation of cases of suspected liver disease in mature horses. Objective: Much of the data gathered during the investigation of suspected hepatopathy cases offers little prognostic guidance and interpretation of such data can be misleading. Methods: The results from a range of common and noninvasive diagnostic techniques applied in 116 mature horses with suspecte...
Bakos Z, Vörös K, Kellokoski H, Reiczigel J.The aim of the study was to evaluate the diagnostic value of thoracic percussion and ultrasonography with the help of distance measurements and statistical methods in the determination of the caudal lung border in horses with recurrent airway obstruction (RAO). Examinations were performed on 11 healthy, warm-blooded horses of different breeds, age and grade of disease. First, the caudal lung border was determined by the traditional indirect percussion method in the 10th, 12th, 14th and 16th intercostal spaces at the end of inspiration and expiration on both sides of the thorax. To apply standa...
Christley RM, French NP.The topology of the network of contacts between individuals has important effects on infectious disease dynamics within a population. Here we examine for the first time a network of contacts between training yards that occurred through racing. Objective: To explore the topology of this network and to consider the effects of the network on the potential for disease transmission. Methods: Race data from one week was analysed. Contacts were defined as occurring between trainers that raced horses in the same race and hence one trainer could contact another trainer several times. A connection was s...
Bøgh IB, Brink P, Jensen HE, Lehn-Jensen H, Greve T.In the mare, ultrasound-guided transvaginal oocyte recovery and transfer might offer a way to circumvent the demanding procedures of in vitro embryo production. Before clinical application, the possible consequences for subsequent fertility have to be considered. Objective: To examine ovarian function and morphology in mares after repeated follicular punctures. Methods: A total of 14-26 follicular puncture sessions were conducted on each of 4 Norwegian pony mares over a period of 8 years. The ovaries of these mares were recovered by bilateral ovariectomy or at post mortem and subjected to macr...
Dunkel B, McKenzie HC.Sporadic measurement of serum triglycerides in depressed and inappetant clinically ill horses revealed severe hypertriglyceridaemia without visible evidence of lipaemia on several occasions, leading to the inclusion of serum triglyceride concentrations in the routine serum biochemistry evaluation of our hospital. Since then, more cases have been identified and treated for hypertriglyceridaemia, raising questions about the prevalence, predisposing factors and significance of these findings. Objective: 1) Severe hypertriglyceridaemia without visible opacity of the serum occurs more commonly in c...
Seahorn JL, Slovis NM, Reimer JM, Carey VJ, Donahue JG, Cohen ND.To identify factors significantly associated with an epidemic of fibrinous pericarditis during spring 2001 among horses in central Kentucky. Methods: Case-control study. Methods: 38 horses with fibrinous pericarditis and 30 control horses examined for other reasons. Methods: A questionnaire was developed to solicit information regarding a wide range of management practices and environmental exposures from farm owners or managers. Results: The following factors were found in bivariate analyses to be significantly associated with an increased risk of pericarditis: being from a farm with mares an...
Kweon CH, Kwon BJ, Ko YJ, Kenichi S.VP7, the sero-group common antigen, of African horsesickness virus (AHSV-4) was expressed in insect cells by recombinant baculovirus. To develop a specific diagnostic method, monoclonal antibody (Mab) against VP7 was prepared and investigated as diagnostic reagent with the baculovirus expressed VP7. However, the Mab against VP7 of AHSV cross-reacted with Chuzan virus by the indirect immunofluorescence assay (IFA), confirming the presence of conserved domain of VP7 among Orbiviruses. This study describes two types of ELISA; Mab linked indirect (I-ELISA) and competitive-ELISA (C-ELISA) using bac...
Murrell JC, Johnson CB, White KL, Taylor PM, Haberham ZL, Waterman-Pearson AE.To identify changes in the amplitude spectrum of the electroencephalogram (EEG) during a standardized surgical model of nociception in horses. Methods: Thirteen entire male horses and ponies referred to Division of Clinical Veterinary Science, Bristol (n = 9) and Department of Clinical Veterinary Medicine (n = 4) for castration. Methods: Following pre-anaesthetic medication with acepromazine, anaesthesia was induced with guaiphenesin and thiopental and maintained with halothane in oxygen. The EEG was recorded continuously using subcutaneous needle electrodes. Additional monitoring comprised EC...
Götzen N, Cross AR, Ifju PG, Rapoff AJ.We investigated the microstructural basis of a reduced stress concentration around the primary nutrient foramen of the equine third metacarpus. We quantified the spatial variations of compositional parameters (mineral content, volume fraction, histological architecture, and osteonal trajectories) from microradiographs and polarizing microscopic images of thin sections. These variations in composition and organization in turn cause variations in mechanical properties of cortical bone. We modeled the spatially inhomogeneous anisotropic elastic properties based on the measured compositional param...
Soboll G, Whalley JM, Koen MT, Allen GP, Fraser DG, Macklin MD, Swain WF, Lunn DP.Equine herpesvirus-1 (EHV-1) causes serious disease in horses throughout the world, despite the frequent use of vaccines. CTLs are thought to be critical for protection from primary and reactivating latent EHV-1 infections. However, the antigen-specificity of EHV-1-specific CTLs is unknown. The aim of this study was to identify EHV-1 genes that encode proteins containing CTL epitopes and to determine their MHC I (or ELA-A in the horse) restriction. Equine dendritic cells, transfected with a series of EHV-1 genes, were used to stimulate autologous CTL precursor populations derived from previous...
Bailey SR, Katz LM, Berhane Y, Samuels T, De Brauvere N, Marr CM, Elliott J.To measure concentrations of amines formed in the cecum of clinically normal ponies, determine amine concentrations in plasma samples collected in spring and winter, and compare concentrations of amines and serotonin in plasma samples obtained from clinically normal ponies and ponies predisposed to laminitis. Methods: Cecal contents obtained from 10 ponies euthanatized at an abattoir and blood samples obtained from 42 adult ponies. Methods: Cecal contents were assayed for amines by high-performance liquid chromatography (HPLC). Blood samples were collected at various times of the year from 20 ...
Radtke CL, Danova NA, Scollay MC, Santschi EM, Markel MD, Da Costa Gómez T, Muir P.To determine changes in the distal ends of the third metacarpal and metatarsal bones (MCIII and MTIII) of Thoroughbred racehorses that had sustained a catastrophic condylar fracture during high-speed exercise. Methods: Fractured and contralateral MCIIIs and MTIIIs from 11 Thoroughbred racehorses that sustained a displaced condylar fracture during racing, both MCIIIs from 5 Thoroughbred racehorses euthanatized because of a catastrophic injury other than a condylar fracture, and both MCIIIs from 5 horses of other breeds that had not been professionally trained or raced. Methods: Macroscopic obse...
Elliott J, Berhane Y, Bailey SR.To determine in vitro vasoactive potency of monoamines formed in the cecum and found in the systemic circulation of horses. Methods: Segments of digital blood vessels obtained from 6 healthy mixed-breed horses and ponies euthanatized at an abattoir and platelets isolated from 4 healthy ponies. Methods: Paired rings of digital artery and vein from the same horse were examined, and isometric tension was recorded. Concentration-response curves for tryptamine (TRP), tyramine (TYR), phenylethylamine (PEA), isoamylamine (IAA), and isobutylamine (IBA) were obtained. Vasoconstrictor mechanisms were in...
Blackmore CG, Stark LM, Jeter WC, Oliveri RL, Brooks RG, Conti LA, Wiersma ST.After West Nile virus (WNV) was first detected in Florida in July 2001, intensive surveillance efforts over the following five months uncovered virus activity in 65 of the state's 67 counties with 1,106 wild birds, 492 horses, 194 sentinel chickens, and 12 people found infected with the virus. Thirteen of 28 mosquito isolations came from Culex mosquitoes. As seen in the northeastern United States, wild bird mortality was the most sensitive surveillance method. However, unlike the predominantly urban 1999 and 2000 epizootics, the Florida transmission foci were rural with most activity detected ...
Nadler SA, Carreno RA, Adams BJ, Kinde H, Baldwin JG, Mundo-Ocampo M.Phylogenetic relationships among six isolates of Halicephalobus gingivalis (Stefanski, 1954), a species with pathogenic potential in horses and humans, were evaluated using DNA sequences from the nuclear large-subunit ribosomal RNA (LSU rDNA) gene. Sequences from nematodes obtained from in vitro cultures (soil or clinical sources), or isolated from infected horse tissues, were compared. Gene sequences from a fatal equine clinical case from southern California and a free-living isolate recovered from southern California soil showed no fixed differences. Sequences from isolates representing two ...
Dowdall SM, Proudman CJ, Love S, Klei TR, Matthews JB.Cyathostomins are important equine gastrointestinal parasites. Mass emergence of mucosal stage larvae causes a potentially fatal colitis. Mucosal stages are undetectable non-invasively. An assay that would estimate mucosal larval stage infection would greatly assist in treatment, control and prognosis. Previously, we identified two putative diagnostic antigens (20 and 25 kDa) in somatic larval preparations. Here, we describe their purification and antigen-specific IgG(T) responses to them. Western blots confirmed the purity of the antigens and showed that epitopes in the 20 kDa complex were sp...
This report summarizes West Nile virus (WNV) surveillance data reported to CDC through ArboNET as of 3 a.m., Mountain Daylight Time, September 10, 2003.
Chen C, Montelaro RC.Synthesis of Gag-Pol polyproteins of retroviruses requires ribosomes to shift translational reading frame once or twice in a -1 direction to read through the stop codon in the gag reading frame. It is generally believed that a slippery sequence and a downstream RNA structure are required for the programmed -1 ribosomal frameshifting. However, the mechanism regulating the Gag-Pol frameshifting remains poorly understood. In this report, we have defined specific mRNA elements required for sufficient ribosomal frameshifting in equine anemia infectious virus (EIAV) by using full-length provirus rep...
Abraham G, Kottke C, Dhein S, Ungemach FR.Although in the respiratory system there is great therapeutic interest in manipulating and understanding the beta-adrenoceptor-G-protein-adenylate cyclase (AC) signal transduction pathway, little is known on segmental differences among lung, bronchus, and trachea with regard to the receptor concentration and interaction to G-proteins and coupling to AC. In this study, patterns of distribution and absolute quantities of beta-adrenoceptor subtypes beta(1) and beta(2) were determined in membranes of equine lung parenchyma, bronchial and tracheal epithelium with the underlying smooth muscle by sat...
Pirie RS, Dixon PM, McGorum BC.Mould extract inhalation challenges have been used extensively in the investigation of heaves. Such challenges have induced pulmonary neutrophilic inflammation and dysfunction, consistent with, but less severe than the natural disease. However, the method of mould extract production is likely to result in endotoxin contamination. Objective: To investigate whether insufficient dose delivery was responsible for the shortfall in response to inhaled extract compared with natural disease, and whether endotoxin contamination of mould extract contributed to the pulmonary inflammation and dysfunction....
Cook RF, Cook SJ, Berger SL, Leroux C, Ghabrial NN, Gantz M, Bolin PS, Mousel MR, Montelaro RC, Issel CJ.Pathogenicity was reportedly restored to an avirulent molecular clone of equine infectious anemia virus (EIAV) by substitution of 3' sequences from the pathogenic variant strain (EIAV(PV)). However, the incidence of disease in horses/ponies was found to be significantly lower (P = 0.016) with the chimeric clone (EIAV(UK)) than with EIAV(PV). This was attributable to 3' rather than 5' regions of the proviral genome, where EIAV(UK) differs from the consensus EIAV(PV) sequence by having a 68-bp duplication in the 3' LTR and arginine (R(103)) rather than tryptophan (W(103)) at position 103 in the ...
Mealey RH, Zhang B, Leib SR, Littke MH, McGuire TC.Equine infectious anemia virus (EIAV) is a lentivirus that causes persistent infections in horses. We hypothesized that high-avidity CTL specific for nonvariable epitopes might be associated with low viral load and minimal disease in EIAV-infected horses. To test this hypothesis, memory CTL (CTLm) responses were analyzed in two infected horses with high plasma viral loads and recurrent disease (progressors), and in two infected horses with low-to-undetectable viral loads and mild disease (nonprogressors). High-avidity CTLm in one progressor recognized an envelope gp90 epitope, and the data doc...
Herrera HD, Duchene AG, Croxatto JO, Burgués N, Amusquibar H.Vascular tumors of the conjunctiva in the horse are rare. We present a unique case of an intravascular papillary endothelial hyperplasia of the conjunctiva. Methods: Horse. Methods: Case report. A 6-year-old-mare presented with a red mass in the conjunctiva of the left eye. After complete ophthalmologic examination the lesion was excised. The tissue was processed for light microscopy and studied histopathologically. Results: Pathologic examination revealed a nonencapsulated vascular lesion composed of confluent vascular spaces filled by multiple papillary structures composed of a central colla...
Taniguchi K, Obitsu T, Ohmura H, Hiraga A, Hata H, Aida H, Akiyama K, Tanaka K.A rigid-type of polyethylene T-cannula was fitted into the anterior ileum of six horses in order to improve the cannulation techniques. A piece of polyethylene net was fastened onto the intestinal wall around the cannula to prevent dislodgment of the cannula by promoting a secure adhesion between the ileum and the abdominal wall. The cannula barrel sheathed with silicone tubing was exteriorized through a stab incision at the lateral ventral wall on the transverse line of the second lumber vertebra, and a flange was screwed onto the barrel. The feeding regime gradually increased concentrate wit...
Hoque S, Senba H, Tsunoda N, Derar RI, Watanabe G, Taya K, Osawa T, Miyake Y.To clarify the endocrinological characteristics of the mares with granulosa theca cell tumor (GTCT), peripheral plasma samples from the 6 mares affected with GTCT were collected before and after the surgical removal of the affected ovary. Concentrations of testosterone (T), follicle stimulating hormone (FSH), luteinizing hormone (LH), immunoreactive-inhibin (ir-INH), progesterone (P) and estradiol-17beta (E(2)) in the plasma samples were measured by radioimmunoassay. Before removal of GTCT in all cases, the concentrations of T were significantly higher than those of normal mares at the breedin...
Whittaker AG, Love S, Parkin TD, Duz M, Cathcart M, Hughes KJ.The pH measurement of exhaled breath condensate (EBC) may provide a non-invasive method of assessing the lower airways of horses but the methodology used may influence findings. The aim of this study was to investigate the effect of two sampling devices and three methods of condensation surface cooling (ethanol slush, -100°C; dry ice, -75°C; water ice, 0°C) on EBC pH. Each method was tested 30 times using six healthy ponies. Sample pH was determined before and after de-aeration with argon for 10 min. Sampler design was found to significantly affect pH. Samples collected as a liquid had a si...
Berti A, Liguri G, Stefani M, Nassi P, Ramponi G.Horse muscle acylphosphatase antibodies were obtained by immunizing rabbits with the highly purified antigen cross-linked with glutaraldehyde. Specific antibodies were purified from the immunoglobulin fraction by affinity chromatography using a matrix coupled with the pure antigen as immunoadsorbent. The purified antibodies were partially characterized by immunodiffusion and immunoprecipitin techniques. These antibodies could be used to study aspects of the muscle acylphosphatase structure, localization and other biological properties.
Walthall JC, McKenzie RA.Horses grazing manily Cenchrus ciliaris and/or Panicum maximum var. trichoglume pastures on over 30 properties in southern central Queensland developed lesions of osteodystrophia fibrosa. Horses on individual properties in coastal Queensland grazing Setaria anceps, Brachiaria mutica or Pennisetum clandestinum also developed the disease. Ill-thrift, lameness, and fibrous swellings of nasal bones, maxillae and mandibles were observed. Calcium and phosphorus levels of pasture were normal but all the above pasture species contained oxalates which were suspected of causing the disease.
Pirie RS, Mayhew IG, Clarke CJ, Tremaine WH.Intraoperative brain ultrasonography is commonly used clinically
in human and canine neonates (Johnson and Rumack 1980;
Babock and Han 1981; Cappe and Lam 1985; Hudson et al. 1990,
1991) and a single report exists of its use to assist in defining
hydrocephalus in an equine neonate (Foreman et al. 1983). This
technique has also been reported to be clinically useful in human
adults (Rubenstein et al. 1984) and ultrasound-guided brain biopsy
has also been described in mature dogs (Thomas et al. 1993).
%ours of the central nervous system in the horse are
extremely rare, with the exception...
Te Moller NCR, Pitkänen M, Sarin JK, Väänänen S, Liukkonen J, Afara IO, Puhakka PH, Brommer H, Niemelä T, Tulamo RM, Argüelles Capilla D....Arthroscopic optical coherence tomography (OCT) is a promising tool for the detailed evaluation of articular cartilage injuries. However, OCT-based articular cartilage scoring still relies on the operator's visual estimation. Objective: To test the hypothesis that semi-automated International Cartilage Repair Society (ICRS) scoring of chondral lesions seen in OCT images could enhance intra- and interobserver agreement of scoring and its accuracy. Methods: Validation study using equine cadaver tissue. Methods: Osteochondral samples (n = 99) were prepared from 18 equine metacarpophalangeal joint...
McClanahan S, Hunter J, Murphy M, Valberg S.Propylene glycol and mineral oil are commonly used in the veterinary profession for treatment of bovine ketosis and equine impactions, respectively. Accidental administration of 6.0 ml propylene glycol/kg of body weight in horses causes severe depression, ataxia and malodorous breath and feces. However, appropriate medical therapy can result in successful treatment of this toxicosis.
Okumura M, Asano M, Tagami M, Tsukiyama K, Fujinaga T.Serum concentrations of copper (Cu), zinc (Zn), manganese (Mn), calcium (Ca) and inorganic phosphorus (P), as well as antigenic ceruloplasmin (Cp) and oxidase activity as a functional index for copper metabolism, were measured in 10 foals (5 males and 5 females) and their dams. Samples were harvested from the foals within 1 wk after birth and monthly from 1 to 17 mo of age. Samples were collected from their dams in the perinatal period (monthly from 2 mo before delivery to 5 mo postpartum). Serum oxidase activity, antigenic Cp and Cu in foals were extremely low at 1 wk. Serum Cp had the lowest...
Curling A.Equine recurrent uveitis has traditionally been treated with medical management to reduce ocular inflammation and control pain during a single episode. Newer management methods include surgical options such as cyclosporine implantation and vitrectomy. These methods were developed not only to control inflammation but also to eliminate the underlying cause of uveitis in order to prevent recurrence.
Ohmes CM, Davis EG, Beard LA, Vander Werf KA, Bianco AW, Giger U.Two Quarter horses with weight loss had glucosuria, euglycemia, and a mild metabolic acidosis suggesting a proximal renal tubular defect. Further testing revealed transient generalized aminoaciduria, lactic aciduria, and glucosuria, indicating Fanconi syndrome. Both horses recovered with supportive therapy. This is the first report of acquired Fanconi syndrome in horses. Deux chevaux Quarter horse ayant subi une perte de poids étaient atteints de glucosurie, d’euglycémie et d’une acidose métabolique légère suggérant un défaut tubulaire rénal proximal. De nouveaux tests ont révél...
Hinrichs K, Hunt PR.The ultrasonic appearance of seven cases of granulosa cell tumour is described, and compared with an ovarian haematoma and an ovarian serous cystadenoma. The granulosa cell tumours varied from being uniformly dense to having one or several large fluid filled cysts. Some tumours resembled the haematoma or cystadenoma and also, in some aspects, normal ovarian structures such as corpora haemorrhagica or follicles in early pregnancy. There was no typical ultrasonographic appearance of the granulosa cell tumours which enabled definitive diagnosis. However, ultrasound may be a diagnostic aid when us...
Bernard WV, Williams D, Tuttle PA, Pierce S.A Thoroughbred foal that was born after 305 days of gestation was referred 6 hours after birth. On initial examination, the foal was alert, but weak and unable to stand. Heart rate was 150 beats/min, respiratory rate was 48 breaths/min, and rectal temperature was 33 C. Leukocytosis was detected (26,000 WBC/microliters). Dysuria and passage of red urine was observed approximately 30 hours after admission. Urine collected by free catch had a 3+ reaction for blood on dipstick analysis. Examination of Warthin Starry-stained sections of allantochorion revealed organisms morphologically characterist...
Del Piero F.Two 5-year-old grade male horses presented with epiphora, rhinorrhea, conjunctival and nasal mucosal hyperemia, and dorsal and thoracic macropapular rash. Skin biopsies were collected from the affected areas, and serial sections were evaluated following hematoxylin and eosin and immunoperoxidase histochemistry staining by using a murine monoclonal antibody of the immunoglobulin G2A isotype recognizing the 30-kDa membrane protein of equine arteritis virus (EAV). In both horses, lesions consisted of mild to moderate diffuse superficial dermal edema and vasculitis with mild perivascular lymphocyt...
McKenzie EC.Polyuria and polydipsia provide a diagnostic challenge for the equine clinician. This article describes the various known causes of polyuria and polydipsia in horses and provides a description of a systematic diagnostic approach for assessing horses with polyuria and polydipsia to delineate the underlying cause. Treatment and management strategies for addressing polyuria and polydipsia in horses are also described.
Joubert P, Cordeau ME, Boyer A, Silversides DW, Lavoie JP.Heaves, also known as recurrent airway obstruction, is a common condition of horses characterised by pulmonary neutrophilia and reversible airway obstruction. This study evaluated the role of neutrophils in producing cytokines and chemokines that might be involved in the recruitment and activation of inflammatory cells in horses with heaves. Peripheral neutrophils were isolated from heaves-affected (n = 9) and control (n = 4) horses before and after 5 h of natural inhalation challenge. Expression of mRNA of two pro-inflammatory cytokines, tumour necrosis factor (TNF)-alpha and interleukin (IL)...
Engiles JB.The etiopathogenesis of laminitis is complex and involves multiple tissue types. It may be initiated by biomechanical, traumatic, inflammatory, vascular, toxic, and metabolic factors. Although histopathologic changes occurring within the lamellae of experimental models of laminitis are well described and reported, histopathologic changes occurring in the distal phalanx are not, even though gross and radiographic evidence of disease are often apparent and bony lesions could be considered a significant source of pain. Recent scientific evidence indicates that the microenvironment of bone is an i...