Neurological Disorders and Neurodegenerative Diseases

The induction of a neuropathic state in rats by nerve ligation or constriction is associated with an up-regulation of dynorphin synthesis, reflected by enhanced expression of prepro-dynorphin protein and mRNA, increased dynorphin immunor-eactivity and a greater percentage of spinal neurons receiving dynorphin-immuno-reactive contacts. The presence of dynorphin receptors and dynorphins (and its increased synthesis in neuropathic states) in spinal pathways suggests a role for these peptides in nociception. This assumption is strengthened by the fact that agonists of k receptors posses anti-nociceptive properties. Data on the effects of k receptor agonists in the spinal cord are controversial. While agonists exert no effect on neurons of the dorsal horn, which are electrically stimulated, it has been shown that agonists inhibit depolarization induced by thermal or mechanical nociceptive stimuli. It has also been shown that the intraventricular application of k receptor agonists or their direct application to the periaqueductal gray induces only subtle anti-nociceptive effects, whereas stimulation of supraspinal k receptors is more effective in inhibiting thermal or mechanical nociceptive stimuli. Taken together, the data on k receptors and their possible interaction with dynorphins indicate a considerable degree of functional diversification in nociceptive mechanisms.

It has been demonstrated that relatively low doses of dynorphin produce analgesia, whereas higher doses produce hyperalgesia that persists for greater then 60 days after a single intrathecal injection. This protracted effect appears to be independent of activation of opioid receptors. In addition it has been shown that, under pathological conditions resulting from injury to peripheral nerves, the up-regulation of spinal dynorphin is accompanied by the development of chronic pain states. Thus, the development of chronic pain states can be blocked by anti-dynorphin antiserum (Lai et al. 2001). Thus, dynorphin can have both nociceptive and antinociceptive properties. It is thought that low levels of dynorphin, acting via k receptors, induce analgesia. Higher doses of dynorphin allows dynorphin to interact with multiple sites on the NMDA receptor complex and, thereby, to produce excitatory responses resulting in nociceptive and even toxic effects (Laughlin et al. 2001).

Dynorphins may also play a role in stress, since stress increases dynorphin immunoreactivity in different limbic brain regions and since dynorphin antagonism produces antidepressant-like effects in rats exposed to learned helplessness (an animal model of depression).

It was found that dynorphin modulates neuronal activity in in vitro brain slices of the hippocampus and that dynorphins are released in the hippocampus during complex partial seizures. Since dynorphin potentiates endogenous anti-ictal processes, it was suggested that dynorphin plays a role as an endogenous anticonvul-sant. Thus, there seemed to exist also a role of dynorphins in epilepsy.

Peripheral Neuropathy Natural Treatment Options

Peripheral Neuropathy Natural Treatment Options

This guide will help millions of people understand this condition so that they can take control of their lives and make informed decisions. The ebook covers information on a vast number of different types of neuropathy. In addition, it will be a useful resource for their families, caregivers, and health care providers.

Get My Free Ebook

Post a comment