@article{williams_meyers_braxton_diekman_lascelles_2022, title={Pilot comparison of outcome measures across chemical and surgical experimental models of chronic osteoarthritis in the rat (Rattus norvegicus)}, volume={17}, ISSN={["1932-6203"]}, url={https://doi.org/10.1371/journal.pone.0277943}, DOI={10.1371/journal.pone.0277943}, abstractNote={Relatively little work has evaluated both the disease of osteoarthritis (OA) and clinically-relevant pain outcome measures across different OA models in rats. The objective of this study was to compare sensitivity, pain, and histological disease severity across chemical and surgical models of OA in the rat. Stifle OA was induced in Sprague–Dawley rats via intraarticular injection of monoiodoacetate (MIA) or surgical transection of anterior cruciate ligament and/or destabilization of medial meniscus (ACL+DMM or DMM alone). Reflexive (e.g., mechanical and thermal stimuli) measures of sensitivity and non-reflexive assays (e.g., lameness, static hindlimb weight-bearing asymmetry, dynamic gait analysis) of pain were measured over time. Joint degeneration was assessed histologically. Six-weeks post OA-induction, the ACL+DMM animals had significantly greater visually observed lameness than MIA animals; however, both ACL+DMM and MIA animals showed equal pain as measured by limb use during ambulation and standing. The MIA animals showed increased thermal, but not mechanical, sensitivity compared to ACL+DMM animals. Joint degeneration was significantly more severe in the MIA model at 6 weeks. Our pilot data suggest both the ACL+DMM and MIA models are equal in terms of clinically relevant pain behaviors, but the MIA model is associated with more severe histological changes over time potentially making it more suitable for screening disease modifying agents. Future work should further characterize each model in terms of complex pain behaviors and biochemical, molecular, and imaging analysis of the sensory system and joint tissues, which will allow for more informed decisions associated with model selection and investigative outcomes.}, number={11}, journal={PLOS ONE}, author={Williams, Morika D. and Meyers, Rachel C. and Braxton, Lauryn A. and Diekman, Brian and Lascelles, B. Duncan X.}, editor={Wijnen, AndreEditor}, year={2022}, month={Nov} }
 @misc{williams_lascelles_2020, title={Early Neonatal Pain-A Review of Clinical and Experimental Implications on Painful Conditions Later in Life}, volume={8}, ISSN={["2296-2360"]}, DOI={10.3389/fped.2020.00030}, abstractNote={Modern health care has brought our society innumerable benefits but has also introduced the experience of pain very early in life. For example, it is now routine care for newborns to receive various injections or have blood drawn within 24 h of life. For infants who are sick or premature, the pain experiences inherent in the required medical care are frequent and often severe, with neonates requiring intensive care admission encountering approximately fourteen painful procedures daily in the hospital. Given that much of the world has seen a steady increase in preterm births for the last several decades, an ever-growing number of babies experience multiple painful events before even leaving the hospital. These noxious events occur during a critical period of neurodevelopment when the nervous system is very vulnerable due to immaturity and neuroplasticity. Here, we provide a narrative review of the literature pertaining to the idea that early life pain has significant long-term effects on neurosensory, cognition, behavior, pain processing, and health outcomes that persist into childhood and even adulthood. We refer to clinical and pre-clinical studies investigating how early life pain impacts acute pain later in life, focusing on animal model correlates that have been used to better understand this relationship. Current knowledge around the proposed underlying mechanisms responsible for the long-lasting consequences of neonatal pain, its neurobiological and behavioral effects, and its influence on later pain states are discussed. We conclude by highlighting that another important consequence of early life pain may be the impact it has on later chronic pain states—an area of research that has received little attention.}, journal={FRONTIERS IN PEDIATRICS}, author={Williams, Morika D. and Lascelles, B. Duncan X.}, year={2020}, month={Feb} }
 @article{williams_sommer_meyers_valdivia_nolan_lascelles_2019, title={A novel device to measure static hindlimb weight-bearing forces in pronograde rodents}, volume={328}, url={https://doi.org/10.1016/j.jneumeth.2019.108405}, DOI={10.1016/j.jneumeth.2019.108405}, abstractNote={Joint pain is composed of both spontaneous and movement-induced pain. In animal models, static bodyweight distribution is a surrogate for spontaneous joint pain. However, there are no commercially-available instruments that measure static bodyweight distribution in normal, pronograde rodents. We designed a Static Horizontal Incapacitance Meter (SHIM) to measure bodyweight distribution in pronograde standing rodents. We assessed the device for feasibility, repeatability, and sensitivity to quantify hindlimb bodyweight distribution. Mice and rats with unilateral inflammatory pain induced by subcutaneous injections of capsaicin or Complete Freund’s Adjuvant (CFA) into the plantar surface of the left hind paw were used to measure static weight-bearing. The ability to attenuate inflammatory pain-associated weight-bearing asymmetry was tested by administering a non-steroidal anti-inflammatory drug, meloxicam. The SHIM’s ability to detect significant reductions in limb loading on the injected hindlimb in mice and rats was validated using both acute and sub-chronic pain models. Treatment with meloxicam partially reversed CFA-induced effects. In contrast with assays that measure kinetic or static weight-bearing forces (e.g., walking, or standing at a 45 ° incline), the SHIM allows evaluation of weight-bearing in rodents that are standing at rest in their normal pronograde position. The SHIM successfully detected: (a) asymmetric weight-bearing in acute and sub-chronic pain models; and (b) the analgesic effects of meloxicam. This study provides a novel tool to objectively evaluate limb use dysfunction in rodents.}, journal={Journal of Neuroscience Methods}, publisher={Elsevier BV}, author={Williams, Morika D. and Sommer, Samantha L. and Meyers, Rachel C. and Valdivia, Juan and Nolan, Michael W. and Lascelles, B. Duncan X.}, year={2019}, month={Dec}, pages={108405} }
 @article{oral transmucosal detomidine gel in new zealand white rabbits (oryctolagus cuniculus)._2017, url={http://europepmc.org/articles/PMC5517333}, journal={Journal of the American Association for Laboratory Animal Science : JAALAS}, year={2017}, month={Jul} }
 @article{williams_long_durrant_mckeon_shive_griffith_messenger_fish_2017, title={Oral transmucosal detomidine gel in New Zealand white rabbits (Oryctolagus cuniculus)}, volume={56}, number={4}, journal={Journal of the American Association for Laboratory Animal Science}, author={Williams, M. D. and Long, C. T. and Durrant, J. R. and McKeon, G. P. and Shive, H. R. and Griffith, E. H. and Messenger, K. M. and Fish, R. E.}, year={2017}, pages={436–442} }
 @article{williams_fish_2016, title={A necessary consideration}, volume={45}, number={2}, journal={Lab Animal}, author={Williams, M. D. and Fish, R. E.}, year={2016}, pages={58–58} }
 @article{williams_fish_2016, title={Response to Protocol Review Scenario: A necessary consideration}, volume={45}, ISSN={0093-7355 1548-4475}, url={http://dx.doi.org/10.1038/LABAN.926}, DOI={10.1038/laban.926}, number={2}, journal={Lab Animal}, publisher={Springer Science and Business Media LLC}, author={Williams, Morika D. and Fish, Richard E.}, year={2016}, month={Jan}, pages={58–58} }
 @article{long_williams_savage_fogle_meeker_hudson_2015, title={Probable primary polydipsia in a domestic shorthair cat}, volume={1}, ISSN={2055-1169 2055-1169}, url={http://dx.doi.org/10.1177/2055116915615370}, DOI={10.1177/2055116915615370}, abstractNote={Case summary A 10-month-old neutered male domestic shorthair cat presented with a 4 month history of polyuria and polydipsia. After a thorough diagnostic work-up the only abnormal findings were hyposthenuria and an elevated random plasma osmolality level. Trial therapy with the oral and ophthalmic forms of desmopressin failed to concentrate urine. A modified water deprivation test confirmed the ability to concentrate urine above a urine specific gravity (USG) of 1.035. After transitioning the cat to a higher sodium diet and instituting several enrichment changes to the cat’s environment, average water consumption and urine output levels decreased to almost normal levels and USG increased from 1.006 to 1.022. These findings provide strong evidence that primary polydipsia was the underlying etiology of the cat’s condition. }, number={2}, journal={Journal of Feline Medicine and Surgery Open Reports}, publisher={SAGE Publications}, author={Long, Charles Tyler and Williams, Morika and Savage, Mason and Fogle, Jonathan and Meeker, Rick and Hudson, Lola}, year={2015}, month={Jul}, pages={205511691561537} }
 @article{briley_williams_freire_griffith_lascelles_2014, title={Feasibility and repeatability of cold and mechanical quantitative sensory testing in normal dogs}, volume={199}, ISSN={["1532-2971"]}, url={https://dx.doi.org/10.1016/j.tvjl.2013.10.025}, DOI={10.1016/j.tvjl.2013.10.025}, abstractNote={Feasibility and inter-session repeatability of cold and mechanical quantitative sensory testing (QST) were assessed in 24 normal dogs. Cold thermal latencies were evaluated using a thermal probe (0°C) applied to three pelvic limb sites. Mechanical thresholds were measured using an electronic von Frey anesthesiometer (EVF) and a blunt-probed pressure algometer (PA) applied to the dorsal aspect of the metatarsus. All QST trials were performed with dogs in lateral recumbency. Collection of cold QST data was easy (feasible) in 19/24 (79%) dogs. However, only 18.4%, 18.9% and 13.2% of cold QST trials elicited a response at the medial tibia, third digital pad and plantar metatarsal regions, respectively. Collection of mechanical QST data was easy (feasible) in 20/24 (83%) dogs for both EVF and PA. At consecutive sampling times, approximately 2 weeks apart, the average EVF sensory thresholds were 414 ± 186 g and 379 ± 166 g, respectively, and the average PA sensory thresholds were 1089 ± 414 g and 1028 ± 331 g, respectively. There was no significant difference in inter-session or inter-limb threshold values for either mechanical QST device. The cold QST protocol in this study was achievable, but did not provide consistently quantifiable results. Both mechanical QST devices tested provided repeatable, reliable sensory threshold measurements in normal, client-owned dogs. These findings contribute to the validation of the EVF and PA as tools to obtain repeated QST data over time in dogs to assess somatosensory processing changes.}, number={2}, journal={VETERINARY JOURNAL}, author={Briley, Jessica D. and Williams, Morika D. and Freire, Mila and Griffith, Emily H. and Lascelles, B. Duncan X.}, year={2014}, month={Feb}, pages={245–250} }
 @article{williams_kirkpatrick_griffith_benito_hash_lascelles_2014, title={Feasibility and repeatability of thermal quantitative sensory testing in normal dogs and dogs with hind limb osteoarthritis-associated pain}, volume={199}, ISSN={["1532-2971"]}, url={http://europepmc.org/articles/PMC4484725}, DOI={10.1016/j.tvjl.2013.11.003}, abstractNote={The objectives of this study were to determine whether thermal quantitative sensory testing (QST) can be performed in client-owned dogs, is repeatable and whether QST differs between normal dogs and dogs with hind limb osteoarthritis (OA). This clinical, prospective, observational study used clinically normal dogs (n = 23) and dogs with OA-associated hind limb pain (n = 9). Thermal QST was performed in standing dogs using a high-powered light source delivered by a previously validated system. Dogs were tested on two occasions, 2 weeks apart. Five tests were performed on each hind limb at each time point. Repeated measures analysis of variance was used to evaluate the effects of leg, time point and OA/normal status on thermal threshold latencies (TTL). Additionally, paired t tests were used to compare the TTL of left and right limbs within groups and between time points. Thermal thresholds were successfully measured in 32 client-owned dogs without prior training. TTL were significantly different between normal and OA dogs (P = 0.012). There was no difference between limbs (P = 0.744) or time periods (P = 0.572), when analyzed by repeated measures analysis of variance, and no interactions between group and limb, visit and limb, or visit and group. In conclusion, thermal thresholds can be measured in client owned dogs with no prior training and are repeatable from week to week. Further data are required to determine if OA results in thermal hypoalgesia as measured at the distal hind limb and whether this is an indication of central sensitization.}, number={1}, journal={VETERINARY JOURNAL}, author={Williams, Morika D. and Kirkpatrick, Amy E. and Griffith, Emily and Benito, Javier and Hash, Jon and Lascelles, B. D. X.}, year={2014}, month={Jan}, pages={63–67} }
 @article{dietary beta-glucan leads to increased tnf-alpha production in the lung_2012, url={http://dx.doi.org/10.3844/ajavsp.2012.55.60}, DOI={10.3844/ajavsp.2012.55.60}, abstractNote={Problem statement: Beta (β)-glucan is notable for its ability to stimulate the immune system and as such β-glucan and products containing β-glucan are used as dietary supplements for livestock and companion animals. β-glucan has been shown to activate macrophages and neutrophils and modulate the production of certain cytokines, including the pro-inflammatory cytokine, Tumor Necrosis Factor Alpha (TNF-α). Because TNF-α is a contributing factor in a number of chronic inflammatory diseases and is present at higher concentrations in bronchoalveolar fluid from patients with asthma a preliminary experiment was designed to determine if a diet supplemented with β-glucan leads to increased TNF-α production in response to chitin, an ubiquitous environmental antigen that is associated with airway inflammation. Approach: Mice were divided into two groups. One group was given normal rodent chow and water while the other group was given normal rodent chow and water containing β-glucan (1 mg mL-1) for 14 days. After 14 days, two experimental protocols were conducted to evaluate TNF-α production. In experimental protocol 1, mice were injected intraperitoneally with 4% thioglycollate broth and TNF-α production from the immune cells elicited into the peritoneal cavity was evaluated. In experimental protocol 2, mice were exposed to either chitin or PBS (as a control) via intranasal administration for two consecutive days. Six hours post secondary exposure, Bronchoalveolar Lavage Fluid (BALF) was collected and ELISA for TNF-α performed. Results: TNF-α expression by thioglycollate-elicited cells isolated from animals that consumed β-glucan was greater (27 fold) than controls. Similarly, dietary β-glucan was also associated with increased TNF-α expression (four fold) in the lung, after chitin exposure in vivo. Conclusion: These preliminary results suggest that dietary β-glucan may promote inflammatory responses after exposure to chitin and therefore could be contributing factor to lung inflammation particularly in animals prone to airway inflammatory diseases.}, journal={American Journal of Animal and Veterinary Sciences}, year={2012}, month={Feb} }
 @article{s. d'costa_yoon_kim_motsinger-reif_williams_kim_2012, title={Morphologic and Molecular Analysis of 39 Spontaneous Feline Pulmonary Carcinomas}, volume={49}, ISSN={["1544-2217"]}, url={http://dx.doi.org/10.1177/0300985811419529}, DOI={10.1177/0300985811419529}, abstractNote={The present study was performed to determine the morphologic change and selected molecular features of spontaneous lung tumors in cats examined at the North Carolina State University Veterinary Teaching Hospital. Thirty-nine primary lung carcinomas represented 0.69% of all feline cases admitted to the hospital. Most lung tumors were observed in aged cats ( P < .0001), and no sex predilection was found ( P < .4241). Persian cats with pulmonary carcinoma were overrepresented in the data set, at least 4 times more frequently than other breeds. The histologic tumor types included adenocarcinoma (64.1%), bronchioloalveolar carcinoma (20.5%), and adenosquamous carcinoma (15.4%). Metastasis was observed in about 80% of 39 cases, with decreasing order of intrapulmonary metastasis, intrathoracic carcinomatosis, regional lymph nodes, and distant organs, including digits. The size of the largest tumor mass was significantly associated with metastatic potential ( P < .001). Based on immunohistochemistry, more than 80% (20 of 24) of feline lung tumors were positively labeled with either surfactant protein A or thyroid transcription factor 1. Epidermal growth factor receptor mutant and p53 proteins were detected in approximately 20% (5 of 24) and 25% (6 of 24) of the feline lung tumor cases, respectively. Limited sequencing analysis of K-ras and p53 genes in 3 selected normal and neoplastic lung tissues did not reveal any alteration. Results indicate that primary lung carcinomas are rare but aggressive tumors in cats, thereby warranting further studies on molecular carcinogenesis.}, number={6}, journal={VETERINARY PATHOLOGY}, author={S. D'Costa and Yoon, B. -I. and Kim, D. -Y. and Motsinger-Reif, A. A. and Williams, M. and Kim, Y.}, year={2012}, month={Nov}, pages={971–978} }