Human temporomandibular joint and myofascial pain biochemical profiles: a case-control study.

Neurobiological mechanisms of human musculoskeletal pain are poorly understood. This case-control study tested the hypothesis that biomarkers within temporomandibular muscle and joint disorders (TMJD) subjects' masseter muscles or temporomandibular joint (TMJ) synovial fluid correlate with plasma biomarker concentrations. Fifty subjects were recruited and categorized into TMJD cases (n=23) and pain-free controls (n=27) at the University of Minnesota School of Dentistry. Prior to specimen collection, pain intensity and pressure pain threshold masseter muscles and the TMJs were assessed. We collected venous blood; biopsied masseter muscle; and sampled TMJ synovial fluid on the subjects' side of maximum pain intensity. We assayed these tissues for the presence of nerve growth factor (NGF), bradykinin (BK), leukotreine B(4) (LTB(4) ) and prostaglandin E(2) (PGE(2) ), F(2) -isoprostane (F(2) I) and substance P (SP). The data was analyzed using Spearman Correlation Coefficients. We found that only plasma concentrations of bradykinin statistically correlated with synovial fluid concentrations (ρ=-0·48, P=0·005), but no association was found between pain intensities. The data suggests that biomarkers used to assess TMJD need to be acquired in a site-specific manner. We also discovered that F(2) I concentrations were associated with muscle pain intensity and muscle pressure pain threshold (PTT) (ß=0·4, 95%CI: 0·03-0·8) and joint PPT (ß=0·4, 95%CI: 0·07-0·8) suggesting that muscle oxidative stress is involved in myofascial pain and that F(2) -I may be a biomarker for myofascial pain.

Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury.

Antagonists of glutamate receptors of the N-methyl-d-aspartate subclass (NMDAR) or inhibitors of nitric oxide synthase (NOS) prevent nervous system plasticity. Inflammatory and neuropathic pain rely on plasticity, presenting a clinical opportunity for the use of NMDAR antagonists and NOS inhibitors in chronic pain. Agmatine (AG), an endogenous neuromodulator present in brain and spinal cord, has both NMDAR antagonist and NOS inhibitor activities. We report here that AG, exogenously administered to rodents, decreased hyperalgesia accompanying inflammation, normalized the mechanical hypersensitivity (allodynia/hyperalgesia) produced by chemical or mechanical nerve injury, and reduced autotomy-like behavior and lesion size after excitotoxic spinal cord injury. AG produced these effects in the absence of antinociceptive effects in acute pain tests. Endogenous AG also was detected in rodent lumbosacral spinal cord in concentrations similar to those previously detected in brain. The evidence suggests a unique antiplasticity and neuroprotective role for AG in processes underlying persistent pain and neuronal injury.

Neurogenesis in postnatal rat spinal cord: a study in primary culture.

Spinal cord injuries result in paralysis, because when damaged neurons die they are not replaced. Neurogenesis of electrophysiologically functional neurons occurred in spinal cord cultured from postnatal rats. In these cultures, the numbers of immunocytochemically identified neurons increased over time. Additionally, neurons identified immunocytochemically or electrophysiologically incorporated bromodeoxyuridine, confirming they had differentiated from mitotic cells in vitro. These findings suggest that postnatal spinal cord retains the capacity to generate functional neurons. The presence of neuronal precursor cells in postnatal spinal cord may offer new therapeutic approaches for restoration of function to individuals with spinal cord injuries.

An iconographic program for computer-controlled whole-cell voltage clamp experiments.

A Macintosh-based system is described for performing instrument control, data acquisition and storage operations in single-electrode whole-cell voltage clamp experiments. The system consists of a commercially available voltage clamp amplifier, multifunction input/output (I/O) board, graphical programming language (LabVIEW 2) and custom built 'virtual instrument' (VI). The I/O board is capable of fast (up to 110 ksample/s) multichannel analog-to-digital (A/D) conversion with 12-bit resolution. It can control the gain settings of the clamp unit through digital I/O lines and generate the P/N leak subtraction protocol to eliminate the linear portion of capacitive currents using analog output voltages and gating pulses. Complete voltage clamp protocols can be implemented using the on-screen front panel controls of the VI. It enables the user to visualize the acquired data, to graph sets of current-voltage (I-V) relations or to fit single-exponential functions to one current trace. To evaluate the adequacy of whole-cell recording, the total membrane capacitance (Cm), the series resistance (Rs) and the time constant (tau c) of the decay of the capacitive current are calculated using the single-exponential function fit to the data. The system is particularly well suited to the study of large quantities of transmembrane I-V relationships. Source code for the crucial elements of the VI as well as sample recordings from a cultured spinal cord neuron, illustrating system operation, are presented.

Anti-nociceptive effect of tricyclic anti-depressants following intrathecal administration.

The anti-nociceptive effects of three tricyclic anti-depressants (desipramine, protriptyline, fluoxetine) were evaluated in mice following intrathecal administration. Nociceptive behavior was produced by intrathecal administration of Substance P and measured for 60 seconds following subcutaneous and intrathecal administration of vehicle and increasing doses of the drugs being tested. Systemically administered protriptyline produced dose related antinociception in this paradigm. A similar effect was seen following systemic desipramine; while fluoxetine was inactive systemically. Both protriptyline and desipramine given intrathecally were antinociceptive while fluoxetine had a biphasic effect, being analgesic only at low doses. These results indicate that tricyclic antidepressants may produce analgesia at the spinal level in rodents. This action may be related to the therapeutic success of tricyclic antidepressants in chronic pain syndromes.