Glutamate and capsaicin-induced pain, hyperalgesia and modulatory interactions in human tendon tissue

Experimental glutamate and capsaicin-induced pain has not been described in tendon tissue despite the implications of addressing these receptors in pain management strategies. This study investigated pain induction and modulatory interactions by injecting glutamate (0.5 ml, 1 M) and capsaicin (0.5 ml, 5 microg, 33 microM) to human tendon tissue. Following the initial glutamate or capsaicin injection, a second injection of either glutamate (following capsaicin), capsaicin (following glutamate) or hypertonic saline (after both glutamate and capsaicin) was given. Twelve male volunteers participated. Subjects had four sequences of injections to tibialis anterior tendon over two sessions 1 week apart. Pain intensity responses were scored on a visual analogue scale (VAS). Pressure pain thresholds (PPTs) were assessed before, during and after pain induction. Capsaicin caused significantly higher peak pain scores compared to glutamate (P < 0.003) whilst glutamate pain was of significantly longer duration (P < 0.0003). Capsaicin following glutamate resulted in significantly higher average VAS scores 180-450 s after injection compared to capsaicin as primary injection (P < 0.05). PPTs were significantly reduced during capsaicin pain (72 +/- 5 and 80 +/- 6% of pre-pain values at the injection site and 2 cm proximal, P < 0.002). Following capsaicin, hypertonic saline and glutamate showed significant reductions in PPT at the same sites and to a similar degree compared to baseline (P < 0.002). The results indicate in tendon tissue a facilitation of response to capsaicin injection following glutamate injection. PPTs were only reliably reduced by capsaicin injection. These results emphasize the possible importance of peripheral glutamate receptor antagonists in pain management in musculoskeletal conditions.