Neuropathic changes in equine laminitis pain (original) (raw)

Assessing Practical Markers for Their Suitability in Estimating the Pain Experienced by Horses with Laminitis

2013

The assessment of pain experienced by horses is complex, often inaccurate, and varies widely among practitioners. During laminitis it is supposed that horses suffer severely from pain. It would be ideal if there were an accurate, reliable and sensitive method of assessing this pain as the condition progresses, and as treatment is applied, to improve the condition of the horse. This work considers various parameters and their suitability as markers to assess the pain experienced by horses undergoing treatment for laminitis. Fourteen horses were assessed during their treatment period. Heart rate, respiration rate and hoof temperature were all significantly correlated with the Obel grading score for lameness. Other parameters, including body temperature, digital pulse and behavioural attitude were not. The horses improved their lameness grade over the period of the trial. It is concluded that the use of the simple practical measures described may be usefully applied by owners and pract...

Pain-associated changes in the dorsal root ganglia of laminitic horses

Journal of Equine Veterinary Science, 2013

Tail amputation by tail docking or as an extreme consequence of tail biting in commercial pig production potentially has serious implications for animal welfare. Tail amputation causes peripheral nerve injury that might be associated with lasting chronic pain. The aim of this study was to investigate the short-and long-term effects of tail amputation in pigs on caudal DRG gene expression at different stages of development, particularly in relation to genes associated with nociception and pain. Microarrays were used to analyse whole DRG transcriptomes from tail amputated and sham-treated pigs 1, 8, and 16 weeks following tail treatment at either 3 or 63 days of age (8 pigs/treatment/age/time after treatment; n = 96). Tail amputation induced marked changes in gene expression (up and down) compared to sham-treated intact controls for all treatment ages and time points after tail treatment. Sustained changes in gene expression in tail amputated pigs were still evident 4 months after tail injury. Gene correlation network analysis revealed two co-expression clusters associated with amputation: Cluster A (759 down-regulated) and Cluster B (273 up-regulated) genes. Gene ontology (GO) enrichment analysis identified 124 genes in Cluster A and 61 genes in Cluster B associated with both "inflammatory pain" and "neuropathic pain." In Cluster A, gene family members of ion channels e.g., voltage-gated potassium channels (VGPC) and receptors e.g., GABA receptors, were significantly down-regulated compared to shams, both of which are linked to increased peripheral nerve excitability after axotomy. Up-regulated gene families in Cluster B were linked to transcriptional regulation, inflammation, tissue remodeling, and regulatory neuropeptide activity. These findings, demonstrate that tail amputation causes sustained transcriptomic expression changes in caudal DRG cells involved in inflammatory and neuropathic pain pathways.

Molecular and cellular mechanisms of nociception in equine laminitis : purinergic P2X receptors expression and distribution

2013

Equine laminitis manifests as a painful condition of the foot and is characterised by disruption of the dermo-epidermal lamellar bond within the equine hoof. Chronic pain in laminitis leads to debilitation and if unchecked euthanasia of the horse and is therefore a significant welfare issue for horses worlwide. P2X receptors are shown to have a pivotal role in pain pathways as well as other tissue functions making them attractive candidates for research in naturally occurring diseases such as equine laminitis. In this study, the presence and distribution of P2X receptors in tissues of the equine digit and its associated vasculature and innervation was investigated. The investigation was extended to tissues from horses suffering from naturally occurring chronic active lamintis in an attempt to identify changes in distribution or expression of the receptors in these tissues. Finally, the functionality of the P2X receptors expressed in equine nervous tissue was investigated. Gene expre...

Investigation of Potential Serum Biomarkers for the Diagnosis of Chronic Back Pain in Horses

Macedonian veterinary review, 2023

Back pain is one of the most common triggers of performance failure in athletic and riding horses. Diagnosis of equine back pain has been very challenging for equine practitioners, particularly in chronic cases. Therefore, the identification of blood biomarkers would facilitate the clinical differentiation of chronic back pain. This study aimed to investigate serum biomarkers of glial cell activation, axonal damage, and inflammation for the diagnosis of equine chronic back pain. Serum samples from forty horses comprising chronic back pain (CBP), back pain concurrent with lameness (BPL), lameness (LN), and healthy control (HC) (n=10 per group) were screened for ionized calcium-binding adaptor molecule 1 (Iba-1), glial fibrillary acidic protein (GFAP), phosphorylated neurofilament-H (pNF-H) by ELISA, and proinflammatory cytokines (IL-1β, IL-6, and TNF-α) by multiplex assay. Serum concentrations of GFAP (3.81±1.72 ng/mL) and pNF-H (0.76±0.18 ng/mL) were significantly (p<0.05) higher in horses with CBP when compared with other groups. Iba-1 was not significantly higher in CBP horses. There was no significant difference between the pro-inflammatory cytokines among the groups. The levels of IL-1β, IL-6, and TNF-α were also increased in the CBP than the HC control horses but lower in relation to BPL and LN horses. In addition, serum Iba-1, GFAP, and pNF-H showed a high discriminatory capacity for horses with CBP with high sensitivity (50-100%) and specificity (70-100%). This study provides evidence that serum levels of the GFAP and pNF-H may be useful in the clinical differentiation of horses with chronic back pain.

An update on equine laminitis

Ciência Rural, 2016

ABSTRACT: Laminitis is a severe podal affection, which pathophysiology remains partially renowned. Ischemic, enzymatic, metabolic and inflammatory mechanisms are connected to the development of laminar lesions. However, few therapeutic measures are effective to prevent or control the severity of acute laminitis and its prodromal stage, which often determines serious complications such as rotation and/or sinking of the distal phalanx and even the loss of hoof. The purpose of this study is to compile the actual knowledge in respect to the pathophysiology and treatment of equine laminitis.

Endocrinopathic laminitis in the horse

Clinical Techniques in Equine Practice, 2004

Laminitis represents one of the most common and potentially crippling diseases of the adult horse, often resulting in permanent lameness or the need for euthanasia. Over the past three decades, many studies have focused on equine laminitis, the majority of published research centering on laminitis arising due to gastrointestinal disease, dietary indiscretion, and endotoxemia. (1,2) In order to gain further insights into this serious pathological condition, experimental models of laminitis have been devised, employing the administration of large quantities of starch,(3) soluble products of Black Walnut trees,(4) or plant-derived fructans.(2) In utilizing these models, the assumption is made that laminitis is a degradative inflammatory condition of the hoof lamellar interface which arises due to changes induced in the large intestinal bacterial flora, accumulation of toxic bacterial products, increased colonic permeability, absorption of bacterial products, and consequent cardiovascular perturbations. Absorbed bacterial products that have been implicated in the pathogenesis of laminitis include lipopolysaccharide (LPS),(5) Streptococcus bovis exotoxins,(6,7) and vasoconstrictive amines. (8,9) A substantial body of evidence exists to show that inflammation is a pivotal and essential component of acute laminitis and that inflammatory changes occur early in the course of experimental laminitis, prior to the development of lameness. These changes include: activation of hoof lamellar matrix metalloproteinases,(10) activation of platelets and the formation of neutrophil-platelet aggregates,(11,12) expression of interleukin-1 (13) and increased concentration of endothelin-1 (14,15) in the hoof lamellar interface, increased expression of COX-2 mRNA by vascular smooth muscle cells obtained from digital vessels, (16) absorption of bacterial LPS into the circulation,(5) and the appearance of polymorphonuclear granulocytes in affected lamellae. (17,18) In some cases, laminitis occurs in the absence of gastrointestinal disturbance, endotoxemia, ingestion of Black Walnut toxins, or other pro-inflammatory conditions (such as primary hoof inflammation).(19) Seemingly unprovoked laminitis arising in horses and ponies on grass pasture ("grass founder") has traditionally been attributed to perceived (uncorroborated) high levels of starch in certain grasses ("lush spring pasture") at certain times of the year. Important new information points to a hitherto unrecognized role for nondigestible, but rapidly fermentable plant storage carbohydrates, fructans, in the risk for laminitis in certain pastures.(2) The role of fructans in the pathogenesis of laminitis has been reviewed elsewhere.(2) Risk of laminitis has also been reported as an association with many other conditions including contralateral lameness, ingestion of endophyte-infected Tall Fescue, exertional rhabdomyolysis, obesity, MS, and conditions associated with excess glucocorticoids (GCs). (19)(20)(21)(22) In this paper, we will review the association of laminitis with various disturbances in the endocrinological systems of the horse. Although much has been written regarding the pathophysiology of laminitis arising from inflammatory models, much less information is available regarding laminitis arising from other causative factors. In order to differentiate laminitis occurring in association with pro-inflammatory and intestinal conditions from laminitis developing from putative hormonal influences, the term endocrinopathic laminitis has been adopted.

Laminitis in horses: through the lens of systems theory

Journal of Equine Veterinary …, 2009

Systems theory is a way of describing complex and dynamic relationships. We applied systems theory to the structure and function of the equine foot in an effort to better understand laminitis and, in so doing, reconcile the various theories of its etiopathogenesis and find more universally effective preventive and therapeutic strategies. The foot is described as an open system, and its inherent vulnerabilities are explored. Cascade failure is discussed as a potentially unifying theory of laminitis. The fundamental failure in laminitis is failure of the lamellar dermalÀepidermal bond, but that endpoint can be reached via vascular, enzymatic, inflammatory, or mechanical mechanisms, or any combination thereof. Inflammation is discussed as a common denominator, making anti-inflammatory therapy of greater importance than just pain management. Multimodal anti-inflammatory therapy is discussed, including selective COX-2 inhibitors, heparin, nutraceuticals, and inhibitors of matrix metalloproteinases (MMPs). Multimodal analgesic therapy also is important and may include nonsteroidal anti-inflammatory drugs (NSAIDs), opiates, epidural analgesics, physical therapy, relief of weight bearing, diligent nursing care, deep digital flexor tenotomy, and case-appropriate trimming and shoeing. Preventing laminitis still comes down to risk management: knowing the risk factors applicable to an individual horse and adjusting the management accordingly. Examples include weight management and control of carbohydrate intake in overweight horses and ponies, the use of pergolide in patients with pituitary pars intermedia dysfunction (PPID), and distal limb cryotherapy in high-risk patients. It is anticipated that application of molecular biologic techniques will further advance treatment and prevention of laminitis.

Intra-articular opioid analgesia is effective in reducing pain and inflammation in an equine LPS induced synovitis model

Equine Veterinary Journal, 2010

Reasons for performing study: Intra-articular administration of morphine as a local analgesic and anti-inflammatory drug is widely used in human medicine. In equids, little is known about its clinical analgesic and anti-inflammatory efficacy. Objectives: To use an inflammatory orthopaedic pain model to investigate the analgesic and anti-inflammatory effects of intra-articularly administered morphine as a new treatment modality in horses with acute arthritis.e vj_77 412..419 Methods: In a crossover study design, synovitis was induced in the left or right talocrural joint by means of intra-articular injection of 0.5 ng lipopolyssacharide (LPS). The effect of 120 mg morphine, intra-articularly administered at 1 h after induction of synovitis, was evaluated using both physiological and behavioural pain variables. Synovial fluid was sampled at 0, 4, 8, 28 and 52 h after induction of synovitis and analysed for total protein concentration, leucocyte count and for prostaglandin E2, bradykinin and substance P concentrations by ELISA. Ranges of motion of metatarsophalangeal and talocrural joints were measured as kinematic variables with the horses walking and trotting on a treadmill under sound and lame conditions. Clinical lameness scores and several behavioural variables related to the perception of pain were obtained. Results: LPS injection caused marked transient synovitis, resulting in increased concentrations of inflammatory synovial fluid markers, clinical lameness, joint effusion and several behavioural changes, such as increased time spent recumbent, decreased limb loading at rest and decreased time spent eating silage. Intra-articular morphine resulted in a significant decrease in synovial white blood cell count, prostaglandin E2 and bradykinin levels and improvement in clinical lameness, kinematic and behavioural parameters, compared to placebo treatment. Conclusions: Intra-articular morphine offers potent analgesic and anti-inflammatory effects in horses suffering from acute synovitis. Potential relevance: Local administration of opioids may be useful for horses with acute inflammatory joint pain and offers possibilities for multimodal analgesic therapies without opioid-related systemic side effects.