Timothy J. Ness, M.D., Ph.D.The Ness Lab is led by Timothy J. Ness, M.D., Ph.D.
Our research focuses on the Mechanisms of Urologic-Gastroenterologic Pain. In NIH-funded studies, translational studies related to urinary bladder and colorectal sensation are being performed by measuring psychophysical responses in humans and parallel studies in rodents. Three preclinical models of visceral hypersensitivity are employed: [1] one produced by acute inflammation; [2] one produced by stress-anxiety; and [3] one produced by developmental mechanisms that are initiated by early-in-life inflammatory events or psychological events that lead to altered neurophysiological processing as adults. The potential for similar mechanisms in humans are now supported by epidemiological studies and functional imaging studies. Parallel quantitative sensory testing studies and regional cerebral bloodflow studies using Continuous Arterial Spin-Label functional MRI technologies are probing whether there exist phenotypic subtypes within clinical populations that correspond to the preclinical models.
The precise interplay between excitatory and inhibitory influences that exist at a spinal level are being dissected out using behavioral, neurophysiological (spinal dorsal horn, medullary and thalamic extracellular neuronal studies), neurochemical and immunohistochemical and primary afferent calcium imaging studies in this programmatic line of research. Psychophysical studies have identified deficiencies in endogenous pain control systems related to counterirritation - similar deficits have been identified in preclinical experimental models.
Areas of Interest
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Laboratory Space
Located in UAB's Pittman Biomedical Research Building II (BMRII), the Ness Lab is an 400 sq. ft. contiguous laboratory space.
Within the laboratory are electrophysiology rigs to allow for spinal dorsal horn and brainstem extracellular neuronal recordings as well as myoelectrical activity used to quantify visceromotor responses to visceral stimuli. Most research formally performed in the Ness lab involve whole animals and follow the ethical guidelines for pain research established by the International Association for the Study of Pain. This means animal subjects are anesthetized or are able to escape noxious stimuli.
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Recent Publications
For a full list of publications prior to 2022, see PubMed.
Recent Publications
- Ness TJ, Babi A, Ness ME, DeWitte C. TRPA1 agonists and bladder nociception in female rats suggest potential for nutraceutical benefit from cinnamon. Nutraceuticals 3:165-174, 2023.
- Robbins MT, DeWitte C, Ness TJ. Stress-induced bladder hypersensitivity: effect of corticotropin releasing factor receptors assessed by spinal neurophysiology and neurochemistry. Neuropharmacology 224: 109369, 2023.
- Ness TJ, DeWitte C, Randich A. The double insult of neonatal cystitis plus adult somatic inflammation results in corticotropin releasing factor Type II receptor-dependent bladder hypersensitivity in female rats. J Pain 23: 2167-2178, 2022.
- Ness TJ, DeWitte C, Randich A. Neonatal cystitis leads to alterations in spinal corticotropin releasing factor receptor-type 2 content and function in adult rats following bladder re-inflammation. Brain Res 1788: 147927, 2022.
- Ness TJ, DeWitte C, Robbins MT and DeBerry JJ. Neonatal cystitis alters mechanisms of stress-induced visceral hypersensitivity in rats. Neurosci Letts 778: 136617, 2022.
- Ness TJ, DeWitte C, DeBerry JJ. Spinal neurochemical mechanisms of acute stress-induced visceral hypersensitivity in healthy rats. Neurosci Letts 770: 136401, 2022.
- Clodfelder-Miller B, Ness TJ and DeBerry JJ. Neonatal bladder inflammation results in adult female mouse phenotype with increased frequency and nociceptive responses to bladder filling. Front Syst Neurosci. 16: 858220, 2022.
- Schuster B, Ness TJ and Sellers A. “Pathophysiology of Somatic Versus Visceral Pain” in Banik R. (Ed). Anesthesiology In-Training Exam Review: Regional Anesthesia and Chronic Pain: Springer International Publishing AG: London UK), 2022.
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Active Grants and Other Support
Current R-01
NIDDK-R01DK51413: “Quantitative Studies of Urinary Bladder Sensation.” Ness (PI) 07/25/97 – 06/30/2023 – Current Direct Costs - $220,000/yearPrincipal Investigator
Title: Quantitative Studies of Urinary Bladder Sensation
Major Goals: The proposed studies examining effects of neonatal bladder inflammation in rodent model systems will give insight related to a novel, non-opioid therapeutic mechanism using CRF2R-linked pharmacology. Neural pathways and mechanisms related to secondary insults such as stress and inflammation will be defined and novel expression of CRF2R mechanisms will be explored. An improved understanding of sensory processing related to IC and of urinary bladder sensory pathways and their modulation by acute stress and pharmacological manipulations will result in an increased translation of basic science to therapeutics for bladder pain.
Co-Investigator
Title: Preclinical phenotypic modeling of chronic urologic pelvic pain
Major Goals: The prevalence of urologic chronic pelvic pain syndrome (UCPPS) in the United States is high, ranging from 14- 25% of men and women. The pathology of UCPPS is multifactorial and existing therapies are both limited and unsatisfactory, underscoring the need for preclinical models that are reflective of disease complexity to advance our mechanistic understanding and identify new treatment strategies. To achieve these goals, we propose to systematically phenotype a dual-insult, preclinical model with high relevance to the clinical condition in order to examine promising targetable units that individually or in combination alter the peripheral nervous system and lead to UCPPS.
Significant Contributor
Title: Preclinical phenotypic modeling of chronic urologic pelvic pain
Major Goals: The prevalence of urologic chronic pelvic pain syndrome (UCPPS) in the United States is high, ranging from 14- 25% of men and women. The pathology of UCPPS is multifactorial and existing therapies are both limited and unsatisfactory, underscoring the need for preclinical models that are reflective of disease complexity to advance our mechanistic understanding and identify new treatment strategies. To achieve these goals, we propose to systematically phenotype a dual-insult, preclinical model with high relevance to the clinical condition in order to examine promising targetable units that individually or in combination alter the peripheral nervous system and lead to UCPPS.