| Substance | Source | Effect |
|---|---|---|
| Bradykinin | Macrophages | Activates nociceptors |
| Plasma kininogen | ||
| Serotonin | Platelets | Activates nociceptors |
| Histamine | Platelets Mast cells | Produces vasodilation, edema, and pruritus |
| Potentiates the response of nociceptors to bradykinin | ||
| Prostaglandin | Tissue injury and cyclooxygenase pathway | Sensitizes nociceptors |
| Leukotriene | Tissue injury and lipooxygenase pathway | Sensitizes nociceptors |
| Excess hydrogen ions | Tissue injury and ischemia | Increases pain and hyperalgesia associated with inflammation |
| Cytokines (interleukins, TNF) | Macrophages | Excite and sensitize nociceptors |
| Adenosine | Tissue injury | Pain and hyperalgesia |
| Neurotransmitters (glutamate, substance P) | Antidromic release by peripheral nerve terminals after tissue injury | Substance P activates macrophages and mast cells Glutamate activates nociceptors |
| Nerve growth factor | Macrophages | Stimulates mast cells to release histamine and serotonin Induces heat hyperalgesia Sensitizes nociceptors |
TNF = tissue necrosis factor.