ABSTRACT
Chronic abdominal pain is a common symptom of inflammatory bowel disease and often persists in the absence of gut inflammation. Although the mechanisms responsible for ongoing pain are unknown, clinical and preclinical evidence suggests lumbosacral spinal cord dorsal horn neurons contribute to these symptoms. At present, we know little about the intrinsic and synaptic properties of this population of neurons in either normal or inflammed conditions. Therefore, we developed an in vivo preparation to make patch-clamp recordings from superficial dorsal horn (SDH) neurons receiving colonic inputs in naïve male mice. Recordings were made in the lumbosacral spinal cord (L6-S1) under isoflurane anesthesia. Noxious colorectal distension (CRD) was used to determine whether SDH neurons received inputs from mechanical stimulation/distension of the colon. Responses to hind paw/tail cutaneous stimulation and intrinsic and synaptic properties were also assessed, as well as action potential discharge properties. Approximately 11% of lumbosacral SDH neurons in the cohort of neurons sampled responded to CRD and a majority of these responses were subthreshold. Most CRD-responsive neurons (80%) also responded to cutaneous stimuli, compared with <50% of CRD-non-responsive neurons. Furthermore, CRD-responsive neurons had more hyperpolarized resting membrane potentials, larger rheobase currents, and reduced levels of excitatory drive, compared to CRD-non-responsive neurons. Our results demonstrate that CRD-responsive neurons can be distinguished from CRD-non-responsive neurons by several differences in their membrane properties and excitatory synaptic inputs. We also demonstrate that SDH neurons with colonic inputs show predominately subthreshold responses to CRD and exhibit a high degree of viscerosomatic convergence.
Subject(s)
Action Potentials/physiology , Afferent Pathways/physiology , Colon/physiology , Posterior Horn Cells/physiology , Skin/innervation , Spinal Cord/cytology , Animals , Biophysical Phenomena , Electric Stimulation , Excitatory Postsynaptic Potentials/physiology , Lumbosacral Region , Male , Mice , Mice, Inbred C57BL , Patch-Clamp Techniques , Physical StimulationABSTRACT
Inhibitory synaptic inputs to hypoglossal motoneurons (HMs) are important for modulating excitability in brainstem circuits. Here we ask whether reduced inhibition, as occurs in three murine mutants with distinct naturally occurring mutations in the glycine receptor (GlyR), leads to intrinsic and/or synaptic homeostatic plasticity. Whole cell recordings were obtained from HMs in transverse brainstem slices from wild-type (wt), spasmodic (spd), spastic (spa), and oscillator (ot) mice (C57Bl/6, approximately postnatal day 21). Passive and action potential (AP) properties in spd and ot HMs were similar to wt. In contrast, spa HMs had lower input resistances, more depolarized resting membrane potentials, higher rheobase currents, smaller AP amplitudes, and slower afterhyperpolarization current decay times. The excitability of HMs, assessed by "gain" in injected current/firing-frequency plots, was similar in all strains whereas the incidence of rebound spiking was increased in spd. The difference between recruitment and derecruitment current (i.e., ΔI) for AP discharge during ramp current injection was more negative in spa and ot. GABAA miniature inhibitory postsynaptic current (mIPSC) amplitude was increased in spa and ot but not spd, suggesting diminished glycinergic drive leads to compensatory adjustments in the other major fast inhibitory synaptic transmitter system in these mutants. Overall, our data suggest long-term reduction in glycinergic drive to HMs results in changes in intrinsic and synaptic properties that are consistent with homeostatic plasticity in spa and ot but not in spd. We propose such plasticity is an attempt to stabilize HM output, which succeeds in spa but fails in ot.
Subject(s)
Motor Neurons/physiology , Mutation/genetics , Neuronal Plasticity/genetics , Receptors, Glycine/genetics , Synapses/genetics , Age Factors , Animals , Animals, Newborn , Brain Stem/cytology , Female , Glycine Agents/pharmacology , In Vitro Techniques , Inhibitory Postsynaptic Potentials/genetics , Male , Membrane Potentials/genetics , Mice , Mice, Inbred C57BL , Mice, Transgenic , Neural Inhibition/drug effects , Neural Inhibition/genetics , Neuronal Plasticity/drug effects , Patch-Clamp TechniquesABSTRACT
A 27-year-old woman presented with metastatic follicular carcinoma of thyroid cell type. Assessment was complicated by recent surgery for "benign" struma ovarii. She underwent total thyroidectomy which failed to show a neoplasm, leaving the struma ovarii as the likely source of the metastasis.
Subject(s)
Adenocarcinoma, Follicular/secondary , Bone Neoplasms/secondary , Ovarian Neoplasms/pathology , Spinal Fractures/pathology , Struma Ovarii/secondary , Thoracic Vertebrae/injuries , Thyroid Neoplasms/pathology , Adenocarcinoma, Follicular/pathology , Adenocarcinoma, Follicular/surgery , Adult , Biopsy, Needle , Bone Neoplasms/pathology , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Ovarian Neoplasms/surgery , Radionuclide Imaging , Risk Assessment , Struma Ovarii/pathology , Struma Ovarii/surgery , Thoracic Vertebrae/pathology , Thyroid Function Tests , Thyroid Neoplasms/diagnostic imaging , Thyroid Neoplasms/surgery , Thyroidectomy , Treatment OutcomeABSTRACT
Clofazimine, a commonly used anti-lepromatous drug, is now being prescribed for the treatment of pyoderma gangrenosum, a complication of inflammatory bowel disease. This drug can cause an obstructive exacerbation of Crohn's disease. Surgeons should be aware of the orange/black discolouration of the bowel, which may mimic ischaemia macroscopically. A case, the first reported in Australia, is described and the literature discussed.
