Acidic buffer induced muscle pain evokes referred pain and mechanical hyperalgesia in humans

Abstract

While tissue acidosis causes local deep-tissue pain, its effect on referred pain and mechanical muscle hyperalgesia is unknown. The aim of this study was to investigate a human experimental acidic muscle pain model using a randomized, controlled, single-blinded study design. 72 subjects (36 female) participated in three visits, each involving one 15 min intramuscular infusion into the anterior tibialis muscle: acidic phosphate buffer (5.2 pH) at 40 ml/hr (N=69) or 20 ml/hr (N=54), normal phosphate buffer (7.3 pH) at 40 ml/hr (N=70), or isotonic saline at 40 ml/hr (N=19). Pain ratings and pressure sensitivity of superficial and deep tissues were assessed before, during, and 20 min after infusion. Acidic buffer produced light to moderate, rate-dependent, muscle pain (not sex-dependent) compared to the control infusions, that referred pain to the ankle in 80% of women and 40% of men. Pain did not vary across selfreported menstrual phases. Pressure pain thresholds (PPTs) were reduced over the infused muscle with acidic infusion, defined as primary mechanical hyperalgesia. PPTs decreased at the ankle in those with referred pain in response to acidic buffer, i.e. referred mechanical hyperalgesia, but not at the foot. No pain or changes in PPTs occurred in the contralateral leg. These results demonstrate muscle acidosis can lead to local and referred pain and hyperalgesia, with significant sex differences in development of referred pain.

Interpreting Joint Pain: Quantitative Sensory Testing in Musculoskeletal Management

“…The lack of change in PPTs at remote sites may signify that more persistent changes in the nociceptive pathways (ie, nonspecific widespread pain) had not taken place. 40 This is consistent with the findings of Frey-Law et al, 14 who, following induced muscle pain, demonstrated decreased PPTs at the site of induced pain and within the area of pain expansion (ie, regional central sensitization) but not at remote sites.…”

Human Experimental Pain Models for Assessing the Therapeutic Efficacy of Analgesic Drugs

“…Examples given are NGF, hypertonic saline, capsaicin, glutamate, bradykinin, serotonin, histamine, prostaglandin, ATP, and phosphate buffer. In this review, only the most widely used methods are described, and the reader is referred to other papers for more specific information (Babenko et al, 1999a,b;GravenNielsen and Arendt-Nielsen, 2003;Mørk et al, 2003;Frey Law et al, 2008). Each substance is described individually and general advantages and limitations are given at the end of this section.…”

Basic aspects of musculoskeletal pain: from acute to chronic pain

“…63 Recently, this observation has been confirmed in humans where intramulcular injection of an acidic buffer induced mechanical muscle hyperalgesia. 64 Tissue acidosis is an important feature in many clinical conditions. 65 This observation has prompted the pharmaceutical industry to start the development of activation of acid-sensing ion channel receptor antagonists, and the acid model can act as a biomarker in this area.…”