Areas of Capsaicin-Induced Secondary Hyperalgesia and
Allodynia Are Reduced by a Single Chiropractic
Adjustment: A Preliminary Study

This section is compiled by Frank M. Painter, D.C.
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FROM:   J Manipulative Physiol Ther. 2004 (Jul);   27 (6):   381–387 ~ FULL TEXT

Parvaneh Mohammadian, PhD, Antonio Gonsalves, DC, Chris Tsai, DC
Thomas Hummel, MD, Thomas Carpenter, DC

School of Medicine,
University of California,
Los Angeles, Calif 90024, USA.

INTRODUCTION:   The aim of the study was to investigate the hypoalgesic effects of a single spinal manipulation treatment on acute inflammatory reactions and pain induced by cutaneous application of capsaicin.

METHODS:   Twenty healthy subjects participated in the experiment, which consisted of 2 sessions. In both sessions, following control measurements, topical capsaicin was applied to the right or left forearm to induce cutaneous inflammatory reactions. The cream was removed after 20 minutes. Then subjects received either spinal manipulation treatment (SMT) or "nonspinal manipulation treatment" (N-SMT), respectively. In control as well as pretreatment and posttreatment intervals, the following tests were performed: measurement of the areas of mechanical hyperalgesia and stroking allodynia, assessment of spontaneous pain, and measurement of blood flow.

RESULTS:   The results confirmed that topical capsaicin induced inflammatory reactions based on occurrence of hyperalgesia and allodynia, augmented pain perception, and increased blood flow following capsaicin application compared with the control session. When compared with N-SMT, spontaneous pain was rated significantly lower post-SMT (P <.014). In addition, areas of both secondary hyperalgesia and allodynia decreased after SMT (hyperalgesia: P <.007; allodynia: P <.003). However, there was no significant treatment effect for local blood flow.

CONCLUSION:   These results suggest hypoalgesic effects following a single SMT. As local vascular parameter was not affected by the single SMT, the hypoalgesic effects appear to be due to central mechanisms.

Keywords:   Chiropractic Manipulation, Hyperalgesia, Allodynia, Pain

From the Full-Text Article:


Numerous studies have investigated the basic mechanisms underlying spinal manipulation treatment (SMT) on pain and inflammatory reactions. [1–5] Vernon et al [2] demonstrated that the pain-relieving effect of manipulation is partly due to a short-term increase of beta-endorphin levels. Subsequent studies failed to replicate these findings while demonstrating hypoalgesic effects of SMT. [3, 4] Furthermore, plasma cortisol and adrenocorticotropic hormone (ACTH) levels did not differ pre-SMT and post-SMT and also when compared with sham treatment. [3] Salivary cortisol level was also shown to remain constant following SMT. [5]

Using visual analog scales, menstrual distress questionnaire, and prostaglandin plasma levels, Kokjohn et al [6] demonstrated in menstruating women that both pain and menstrual distress were significantly reduced following SMT. In this study, the authors also showed a significant reduction of prostaglandin plasma level in the sham group, indicating that a placebo effect was associated with a single sham intervention.

The conflicting results described above clearly indicate that further studies are needed to investigate the physiological mechanisms underlying the effects of spinal manipulation on pain perception and inflammatory reactions. In all recent studies, either patients or healthy volunteers were tested. However, SMT has not been examined in experimental models of human pain/inflammation. Among such models that have been successfully applied to induce inflammatory reactions and pain is the intradermal or topical application of capsaicin, the active ingredient of chili pepper. [7–15] This technique induces a controlled neurogenic inflammation that allows repetitive and gradual assessment of both sensory and local vascular changes. Capsaicin predominantly activates nerve endings of unmyelinated nociceptive afferents. It causes neuropeptide release (such as substance P), resulting in the development of many signs of acute inflammation, eg, hyperalgesia (an increased response to previously noxious stimuli) and allodynia (pain perception induced by innocuous stimuli), vasodilation, increased blood flow, and elevated skin temperature. [16, 17]

The aim of the study was to investigate the hypoalgesic effects of a single SMT on acute inflammatory reactions and pain induced by capsaicin. These effects were assessed by measuring both sensory (allodynia, hyperalgesia, spontaneous pain intensity) and local vascular parameters (blood flow).


As expected, topical capsaicin induced primary hyperalgesia in the application area and secondary hyperalgesia outside that area. While the local vascular parameter blood flow was not affected by a single SMT, the results indicated that sensory parameters (spontaneous pain perception and areas of both secondary hyperalgesia and allodynia) were significantly altered after spinal manipulation compared with nonspinal manipulation treatment (N-SMT). These results clearly demonstrated that in contrast to the N-SMT condition, a single spinal manipulation triggered hypoalgesic effects.

In line with these findings, Glover et al [25] also reported a significant reduction of the size of pinprick pain following manipulation compared with a control group. Another study demonstrated the hypoalgesic effect of spinal manipulation on patients with acute low back pain. [4] Terrett and Vernon [26] reported a statistically significant increase of cutaneous pain thresholds in subjects receiving spinal manipulation compared with a control group. This finding was explained as an inhibitory effect of manipulation on spinal dorsal horn neurons.

In the present study, local blood flow was not affected by a single SMT. However, significant changes were observed on sensory parameters, supporting the hypothesis of centrally mediated effects of a single SMT. It is well known that secondary hyperalgesia appears to be due to central sensitization of the spinal dorsal horn neurons, [8–10] while primary hyperalgesia is caused by nociceptor sensitization. [27, 28] It has also been discussed that mechanisms underlying allodynia are centrally mediated. [15, 29, 30] Our findings also confirm the view that the hypoalgesic effects of a single SMT might be due to central modulation. These effects could also be explained as a result of a stress reaction caused by spinal manipulation treatment. Nonetheless, the findings of previous studies led to inconclusive results in terms of plasma cortisol level. [2–5] Other studies discussed that spinal manipulation stimulates mechanoreceptors of the spinal joints, resulting in afferent discharges and subsequently causing inhibitory reactions on the dorsal horn neurons. [31, 32] Vicenzino et al [33] demonstrated also a strong correlation between hypoalgesic and sympathoexcitatory effects, suggesting that a central control mechanism might be activated by manipulative therapy. While it is obvious that more studies are needed, previous studies as well as the present investigation (a preliminary study with a restricted study design) indicate that hypoalgesic effects of spinal manipulation are more likely mediated through central modulation.


The present study demonstrated hypoalgesic effects of a single spinal manipulation treatment. These effects appear to be due to central rather than peripheral mechanisms, especially as the local vascular parameter blood flow was not affected by single spinal manipulation treatment. The central effects are thought to relate to inhibitory effects in spinal dorsal horn neurons. Nevertheless, more studies are needed to investigate the central mechanisms of SMT.


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