Morphine: axon regeneration, neuroprotection, neurotoxicity, tolerance, and neuropathic pain

Opioids have been used medicinally for millennia for their potent effects on nociception. However, the past 20 years have led to important insights into the influences and mechanisms of opioid actions, which are more extensive than merely analgesia, including human synthesis of opioids, critical roles of opioids during development and following nerve injury, and actions of different opiate alkaloids and their receptors. Due to the vast literature on opioids, the scope of this review has been limited to opioid actions in maintaining neuron viability during development, promoting neurological function following nerve injuries, in inflammation, disease and against ischemia; alleviating neuropathic pain; raising and lowering cellular immunity; and mechanisms modifying morphine tolerance.

Visualization of six unique morphological subpopulations of adult frog dorsal root ganglion neurons at the light microscopic level

Subpopulations of adult frog dorsal root ganglion (DRG) neurons respond to different physiological stimuli, and have unique biophysical and pharmacological properties. Two broad-based subpopulations of DRG neurons appear under phase optics, "large clear" and "small dark" neurons, while immunochemical and electrophysiological techniques allow identification of additional subpopulations. Nevertheless, most studies of DRG neurons involve randomly selected neurons. Under bright field illumination, we found dark and clear DRG neurons are distinctly different, with dark neurons composed of four subpopulations, each with unique numbers and distribution of bright rusty-colored cytoplasmic granules, and statistically significant difference in the soma diameter distribution. The clear neurons are granule-free, but the two subpopulations have statistically significant differences in soma size distributions. Thus, morphological criteria alone allow identification of six distinct subpopulations of DRG neurons in the light microscope, although further studies are required to determine whether they correspond to physiologically different subpopulations of sensory neurons.

Morphological characterization of six subpopulations of adult human DRG neurons at the light microscopic level

Dorsal root ganglion (DRG) neurons are composed of physiologically distinct subpopulations, each responding to a different sensory stimulus. One can morphologically discriminate between two broad populations of adult rat and frog DRG neurons by their appearance under the light microscope. These groups are called large clear and small dark. However, additional subpopulations have not been identified by visual observation. Such identification requires application of immunochemistry or biophysical techniques. Although these are useful techniques, they do not allow the rapid discrimination of different neuron subpopulations, which would be useful for pharmacological studies on unique neuron subpopulations. Such experiments would be greatly facilitated if viable DRG neuron subpopulations could be identified based on their morphology at the light microscopic level. Just as for adult frog and rat DRG neurons, when adult human DRG neurons are observed under phase optics, two subpopulations can be seen, small dark and large light. However, under bright-field illumination, six distinct subpopulations can be distinguished based solely on morphological features. Five subpopulations contain rusty-colored cytoplasmic inclusions with different sized granules and differences in the size and density of the granule clusters, while one is granule-free. Analysis of the soma diameter distribution shows each of the six granule-containing and the non-granule-containing (clear) neuron subpopulations has a statistically significant difference in size distribution. We propose that neurons with different morphologies correspond to unique physiological subpopulations of DRG neurons. Experiments are underway using immunochemical techniques to determine whether neurons with the unique morphologies correspond with unique physiological functions.