The role of peripheral P2X receptors in different painful conditions
| Type of Pain | P2X Receptor Agonist, Allosteric Enhancer, or Antagonist (Route of Application) | Model, Species | Response (Modulation or Induction) | Blockade by Antagonist (Route of Application) | Reference | |
|---|---|---|---|---|---|---|
| Acute pain | Agonists | ATP, α,β-meATP (i.a. or i.art.) | Electrophysiological recordings, anesthetized rat | Firing of articular afferents (↑) | PPADS (i.a.) | Dowd et al., 1998 |
| α,β-meATP, β,γ-meATP (i.pl.) | Electrophysiological recordings, anesthetized rat | Firing of spinal dorsal horn neurons (↑) | Stanfa et al., 2000 | |||
| ATP, α,β-meATP (i.pl.) | Behavioral observation, rat | Paw lifting and licking (↑) | Local anesthetic bupivacaine (i.pl.); desensitization by pretreatment with α,β-meATP or capsaicin (i.pl.) | Bland-Ward and Humphrey, 1997 | ||
| ATP, α,β-meATP (i.pl.) | Mechanical threshold testing, rat | Mechanical allodynia (↑) | PPADS (i.pl.) | Tsuda et al., 2000 | ||
| BzATP (i.pl.) | Behavioral observation, rat | Paw flinching (↑) | TNP-ATP (i.pl.) | Jarvis et al., 2001 | ||
| Cibacron blue (i.pl.) | Behavioral observation, rat | BzATP-induced paw flinching (↑) | Jarvis et al., 2001 | |||
| Cibacron blue (i.pl.) | Formalin test, rat | Early phase of nociceptive behavior (↑) | Jarvis et al., 2001 | |||
| ATP, α,β-meATP, 2-methylthio-ATP (i.pl.) | Behavioral observation and thermal threshold testing, rat | Paw lifting and thermal hyperalgesia (↑) | Hamilton et al., 1999 | |||
| ATP (iontophoresis onto skin) | Pain sensation rating, man | Modest burning pain | Hamilton et al., 2000 | |||
| Antagonists or desensitizing agonists | α,β-meATP pretreatment (i.pl.) | Formalin test, rat | Early phase of nociceptive behavior (N.E.) | Bland-Ward and Humphrey, 1997 | ||
| Suramin (i.pl.) | Formalin test, rat | Early phase of formalin test (N.E.) | Sawynok and Reid, 1997 | |||
| TNP-ATP (i.pl.) | Formalin test, rat | Early phase of nociceptive behavior (↓) | Jarvis et al., 2001 | |||
| Agonists | ATP, α,β-meATP (i.a.) | Electrophysiological recordings in anesthetized rat with CFA-induced arthritis | Firing of articular afferents (↑) similar to non-inflamed rats | PPADS (i.a.) | Dowd et al., 1998 | |
| Cibacron blue (i.pl.) | Formalin test, rat | Late phase of nociceptive behavior (↑) | Jarvis et al., 2001 | |||
| Agonists | ATP, α,β-meATP (i.pl.) | Formalin test, rat | Late phase of nociceptive behavior (↑) | PPADS | Sawynok and Reid, 1997 | |
| ATP, α,β-meATP, 2-meSATP (i.pl.) | Behavioral observation and thermal threshold testing, rat | (↑) Agonist-induced paw lifting and thermal hyperalgesia in rats with carrageenan- or UV-light-induced skin inflammation vs. non-inflamed side | Hamilton et al., 1999 | |||
| ATP (onto blister bases of skin) | Pain sensation rating, man | Painful sensation (↑) | Bleehen and Keele, 1977 | |||
| Inflammatory pain | Agonists | ATP (iontophoresis onto skin) | Pain sensation rating, man | (↑) ATP-induced pain in subjects with UV-light-induced skin inflammation vs. non-inflamed skin | Hamilton et al., 2000 | |
| Antagonists or desensitizing agonists | α,β-meATP pretreatment (i.pl.) | Formalin test, rat | Late phase of nociceptive behavior (N.E.) | Bland-Ward and Humphrey, 1997 | ||
| Suramin (i.pl.) | Formalin test, rat | Late phase of nociceptive behavior (N.E.) | Sawynok and Reid, 199 | |||
| TNP-ATP (i.pl.) | Formalin test, rat | Late phase of nociceptive behavior (↓) | Jarvis et al., 2001 | |||
| Neuropathic pain | Agonists | ATP (i.v.) | Electrophysiological recordings in anesthetized rats after CCI | Ectopic discharges in A fibers at the site of nerve injury (↑) | Reactive blue, but not aminophylline (i.v.) | Chen et al., 1999 |
| Antagonists | Suramin + phentolamine (i.p.) | Mechanical sensitivity testing in rats after SNL | Mechanical allodynia (↓) | Park et al., 2000 | ||
| Visceral pain | Agonists | ATP α,β-meATP (i.a.) | Electrophysiological recordings in anesthetized rat | Mesenteric afferent nerve discharge (↑) | PPADS, suramin (i.v.) | Kirkup et al., 1999 |
| ATP α,β-meATP (i.a.) | Electrophysiological recordings in i.a. perfused rat tongue prep. | Capsaicin-sensitive tongue afferents (↑) | PPADS, suramin (i.a.) | Rong et al., 2000 | ||
| Antagonists or desensitizing agonists | α,β-meATP pretreatment (into bladder) | Electrophysiological recordings in isolated rat bladder-pelvic nerve prep. | Afferent nerve discharge in response to bladder distension (↓) | Namasivayam et al., 1999 | ||
| Suramin (into bladder) | Electrophysiological recordings in isolated rat bladder-pelvic nerve prep. | Afferent nerve discharge in response to bladder distension (↓) | Namasivayam et al., 1999 | |||
i.art., intra-articular; i.pl., intraplantar; prep., preparation; CFA, complete Freund's adjuvant; CCI, chronic constriction sciatic nerve injury; SNL, lumbar 5/6 spinal nerve ligation; ↑, potentiation or induction; ↓, inhibition; N.E., no effect.