The Sympathetic Nervous System Contributes to Capsaicin-Evoked Mechanical Allodynia But Not Pinprick Hyperalgesia in Humans

Abstract

The contribution of the sympathetic nervous system (SNS) to pain, mechanical allodynia (MA), and hyperalgesia in humans is controversial. A clearer understanding is crucial to guide therapeutic use of sympatholytic surgery, blocks, and drug treatments. In rats, capsaicin-evoked MA, and to some extent, pinprick hyperalgesia (PPH), can be blocked with alpha-adrenoreceptor antagonists. In this study, we examined the contribution of the SNS to MA and PPH in normal human subjects by blocking alpha-adrenoreceptors with intravenous phentolamine. In a double-blinded, placebo-controlled, crossover study, subjects were given IV saline or phentolamine, 1 mg/kg over 20 min. Ten minutes after the start of the infusion, subjects received 100 micrograms of intradermal capsaicin on the foot dorsum with the temperature of the injected site clamped at 36 degrees C. The temperature of the uninjected foot was used to monitor the degree of alpha-adrenoreceptor blockade produced by phentolamine. Ongoing pain and MA and PPH areas were measured every 5 min for 60 min. A significantly greater increase in temperature on the uninjected foot was seen during the phentolamine infusion compared with the saline infusion, indicating alpha-adrenergic blockade. Significantly less MA was observed with the phentolamine infusion 10-25 min after capsaicin injection than with the saline infusion. No significant differences in ongoing pain or PPH areas were seen between the two infusions at any time. Our results suggest that capsaicin-evoked MA and PPH have different mechanisms, with the SNS having a role in MA but not in PPH or ongoing pain.

The Sympathetic Nervous System and Pain

“…This effect was reversed by combined blocking of alpha1-and alpha2-receptors (Liu et al 1996;Kinnman et al 1997). However, enhancement of capsaicin induced heat hyperalgesia was also found for other vasoconstrictive agents like vasopressin, angiotensin or the occlusion of blood flow (Drummond 1998), and it was antagonized by vasodilators like nitroprusside (Drummond 1999).…”

Causalgia and reflex sympathetic dystrophy: Does the sympathetic nervous system contribute to the generation of pain?

“…46 Moreover, application of phentolamine, an ␣-adrenoceptor antagonist, reduced pain and mechanical hyperalgesia in capsaicin-sensitized skin. 90,101 However, when sympathetic cutaneous vasoconstrictor activity was modulated in physiological ranges by thermoregulatory reflexes, it did not measurably influence capsaicin-induced pain. Further- more, activation of skin sympathetic vasoconstrictor neurons does not change the irritant-induced discharge of single microneurographically recorded cutaneous C-nociceptors.…”

Differenzierung peripherer und zentraler antihyperalgetischer Effekte einer systemischen Procaindauerinfusion

“…80 (entsprechen 20 µg) intradermal in die medialen Innenseiten der Unterarme injiziert [16]. Die intradermale Gabe einer Capsaicinlösung führt dosisabhängig zu einem intensiven Brennschmerz und einem durch den Axonreflex vermittelten Erythem.Weiterhin werden in dem die Injektionsstelle umgebenden unbetroffenen Hautareal Allodynie und Pinprickhyperalgesie als Zeichen einer sekundären Hyperalgesie beobachtet [17,19]. Die Intensität des Brennschmerzes wurde mittels einer numerischen Ratingskala (NRS) erhoben, die Endpunkte der Skala wurden durch "keinen Schmerz" (0) und den "größten vorstellbaren Schmerz" (10) definiert.Die Probanden wurden angehalten, die Schmerzhaftigkeit der Capsaicininjektion in den ersten 2 min nach Injektion in Abständen von 15 s und anschließend nach 2, 5, 9 und 12 min zu beurteilen.…”