Neuropathic pain

The Peripheral Neuropathy Solution

The Peripheral Neuropathy Program

Get Instant Access

Neurokinin-1 expressing neurons (NK-1) are situated in the superficial lamina of the spinal dorsal horn, utilize substance P as a neurotransmitter and are responsible for relaying a peripheral nociceptive stimulus to the parabrachial area and hence to the cerebrum. This causes a descending signal to the periaqueductal gray area and hence to the rostroventral medulla causing

Table 11.1 Formulation

5HT3 antagonist

Tablet

Syrup

Lyophilisate

Suppository

Injection

Alosetron

X

Dolasetron

X

X

Granisetron

X

X

Ondansetron

X

X

X

X

X

Palonestron

X

Tropisetron

X

X

activation of descending serotinergic and noradrenergic drives on the spinal dorsal horn which inhibit further spino-cerebral nociceptive signaling.

Experimentally, the function of the NK-1 expressing neurons can be terminated by application of the specific toxin substance P - saponin conjugate. When this is done in animals that have formalin applied to their paws, the second phase of the so-called formalin response is significantly reduced. In this response there is normally an acute nociceptive response (the so-called first phase response) followed by a slower and more prolonged nociceptive response (the second phase) which can be measured behavio-rally by counting, for example, the licking activity by the animal of its paw, or electrophysiologically by measuring the electrical activity in deep dorsal horn cells. Therefore, ablation of NK-1 expressing neurones has an antinociceptive effect, at least with this experimental model. This is reinforced by the fact that in animals bred with genetic absence of NK-1 neurons a similar reduction in the second phase of the formalin response occurs.

In contrast, when a carrageenan model of inflammation is used, depletion of these neurons has no effect suggesting that the role of NK-1 expressing neurons is dependent on the nociceptive stimulus.

When the behavioral or electrophysiological measurements are repeated in animals having formalin application to paws and this time the 5HT3 antagonist ondansetron is applied spinally, an exactly similar reduction in the second phase of the formalin response occurs as when substance P -saponin conjugate is applied. This implies two things:

1 That 5HT3 antagonists may have an analgesic effect.

2 If application of a 5HT3 antagonist reduces spino-cerebral nociceptive signaling when we know that 5HT3 agonists normally have this effect, then it suggests that as well as the well-known bulbo-spinal serotiner-gic inhibitory pathways there may also be descending serotinergic facil-itatory pathways as well.

Clinically it has been shown that a single injection of ondansetron in humans with neuropathic pain resistant to previous pharmacological therapy reduces that neuropathic pain. No longer-term dosing studies nor studies where oral ondansetron or other 5HT3 antagonists are used have been carried out.

Therefore, there is suggestion that clinically ondansetron may reduce neuropathic pain and that there is a logical explanation for why that may occur. Clearly significant work needs to be done to verify this observation. From an entirely practical perspective, ondansetron could be given parenter-ally in patients with acute flare-ups of neuropathic pain or to those in whom the oral route is unavailable. The major drawbacks of treatment are that at present, all 5HT3 antagonists are extremely expensive, to the extent that they probably could not be used in a day-in, day-out basis but may be a useful treatment during a period of flare-up of neuropathic pain. The two major side effects of continued 5HT3 use are headache and constipation.

Was this article helpful?

0 0
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