The opioid and NSAID pathways serve as models for understanding the analgesic effect of new and alternative therapeutics such as pulsed radio frequency energy (PRFE).
Electric and magnetic fields have been used in medicine for the treatment of pain, ablation of tissue, and wound healing for more than 75 years. More recently, pulsed radio frequency energy (PRFE) fields have been used for the treatment of bone healing, pain, and wound healing of soft tissue.
In this review, pulsed radio frequency energy fields will be discussed in relation to use in pain management, with an emphasis on the cellular and molecular mechanisms of action related to the pharmaceutical analgesics.
What Is PRFE?
PRFE refers to non-thermal, non-ionizing, non-contact electromagnetic energy with a carrier frequency of 27.12 MHz, delivered with pulse bursts of 10 µsec to 1 msec at a frequency of 1 to 1000 Hz.
These devices are considered by the FDA to be non-thermal shortwave diathermy devices (category ILX) and have been cleared to market for adjunctive use in the palliative treatment of postoperative pain and edema in superficial soft tissue (Figure 1).
PRFE is to be distinguished from pulsed radio frequency electrical current, a modality with similar nomenclature that has been used broadly in medicine, specifically in nerve ablation and electrosurgery
Pulsed radiofrequency electrosurgical devices use an electrode to directly apply alternating current in the radiofrequency range to tissue in order to cut, vaporize, or ablate. These devices are different in design and operating principle from PRFE, which involves delivery of RF electromagnetic fields by means of a non-contact radiating antenna.
In a recent review of the literature, PRFE was found to be useful in relieving chronic pain associated with oral, plastic, podiatric, gynecologic, and abdominal surgical procedures, as well as pain associated with back and neck trauma and post-traumatic algoneurodystrophy.
Recently, a meta-analysis, which evaluated 25 controlled trials including 16 studies that examined the use of PRFE for reduction of pain, assessed the therapeutic effectiveness of PRFE for both postoperative and non-postoperative pain management
PRFE therapy was found to provide effective pain reduction, relative to controls, that was clinically and statistically significant
Neurological Pathways of Pain Reception and Processing
The induction of pain by noxious stimuli is received by the Aβ nerve fibers, a series of nerve fibers distinct from tactile and proprioceptive receptors. These specialized fibers (unmyelinated C fibers and thinly myelinated Aδ fibers) sense the physiochemical properties of pain stimuli.
Noxious stimuli are then converted to transient receptor potentials, which are further amplified by sodium channels to an action potential.
These peripheral inputs are delivered by nociceptive afferents to glutamatergic synapses in the dorsal horn of the spinal cord
hese sensory inputs to the dorsal horn are then carried by different pathways to the specific processing centers of the brain, such as the lateral thalamus, medial thymus, and limbic structures, each being implicated in different aspects of pain perception.
In contrast to nociceptive sensation of pain, neuropathic pain is the result of damage or insult to the nerve structure itself.11 This type of pain can cause neural supersensitivity and may be associated with inflammation and diabetes. In many instances, this type of pain is accompanied by hyperalgesia.12 Neuropathic pain is usually more difficult to treat and in many cases becomes chronic.
Treatment of Nociceptive and Neuropathic Pain
The standard for the treatment of pain is the use of opioids and non-steroidal anti-inflammatory drugs (NSAIDs). The opioid compounds have a historical basis and have been used for pain treatment for hundreds of years. NSAIDs, as typified by aspirin and acetaminophen, are popular mild analgesics used primarily for treating inflammation and the pain associated with it.
The cellular and molecular mechanisms responsible for the opioid and NSAID analgesic effects will be discussed and compared with what is known about PRFE as a means to determine the possible mechanism of analgesia mediated by electromagnetic fields.
Endogenous Peptide Opioid System
Three classical endogenous opioid peptide families have been identified—the endorphins, enkephalins, and dynorphins.
Considering the large number of opioid peptide ligands, it is not surprising that numerous corresponding opioid receptors have been isolated. There are 3 major opioid receptor families: μ, δ, and κ.
Opioid (endogenous or natural occurring) binding to cognate receptors produces a number of intracellular effects linked to analgesia.
These effects include inhibition of adenyl cyclase activity, activation of K+-linked currents, and suppression of Ca2+ currents. The effect of the K+/Ca2+ ion currents are thought to be responsible for the inhibition of pain transmission in the central nervous system
opioid ligand binding may also activate mitogen-activated protein (MAP) kinases and phospholipase C.
All of these intracellular effects may contribute to opioid inhibition of pain. With the large number of opioid ligand and receptor combinations possible, determining which result in analgesia has been problematic.
Opioids produce their primary analgesic effect by inhibiting the transmission of nociceptive signals from the dorsal horn of the spinal cord to activate the pain control pathways descending from the midbrain to the dorsal horn in the spinal cord
Other sites of action of opioid-induced analgesia may be found in the forebrain and peripherally, especially during inflammatory pain states
NSAID Analgesics and Inflammation
NSAIDs are considered mild analgesics and are particularly effective for pain due to inflammation
Pain due to the hyperalgesia most likely results from stimulation of pain fibers and enhanced excitation of neurons in the spinal cord.
During inflammation, bradykinin, tumor necrosis factor (TNF)–α, interleukin (IL)-1, and other cytokines are released and induce pain by binding to their receptors and eliciting their biological effects, such as the release of prostaglandins (PGs) and substance P, which are also thought to be involved in stimulating pain at the level of the spinal cord
Even more detailed information on the chemical reactions involved with pain can be found in the full article.
PRFE Effective Analgesic
Pulsed radio frequency energy and pulsed electromagnetic field (PEMF) fields are becoming increasingly popular as a treatment for pain caused by inflammation or tissue damage
it is suggested that PRFE may elicit reduction in pain by mechanisms similar to those of the NSAIDs, as well as possibly through endogenous opioid peptide pathways.
The authors propose that the analgesic mechanism of action of PRFE is anti-inflammatory via a Ca+2-mediated pathway involving calmodulin binding.
In vitro studies using human dermal fibroblasts (HDF) and human epidermal keratinocytes (HEK) have determined the effects of PRFE on transcript levels of several key enzymes involved in the inflammatory response.
Both the in vivo and in vitro studies point to anti-inflammatory mechanisms for pain reduction, similar to those found for NSAIDs.
A comparison between the different standard therapeutic treatments for analgesia shows that, at least in part, the mechanism of PRFE is similar to that of the NSAIDs (inhibition of COX and related pathways to inflammation).
By understanding the biological and cellular mechanisms underlying PRFE-mediated effects on inflammation and the pain it causes, it is possible that additional therapeutic applications of PRFE may be uncovered.